ADVANCES IN DIAGNOSTIC UROLOGY EDITED BY JOSEPH J. KAUFMAN, M.D., F.A.C.S. rnoFkssofi of svnc-my /vuolocy SCHOOL OF MEDICINE IJN1VEHS1TY OF CALIFOnNIA AT LOS ANGELES With 14 Contributing Authors LiTTi.r,, nnowN and company BOSTON cnrTvtciiT 0 *>' JOsct>H i. xaifmas At* OJCUTA RttCSArD. SO rA«T Of tlH» BOOK MAT BF ■> FBOnrCCU IS AST fORit WJTIIOII WKIIICS PtRA|. AssocMle Clinical Professor of Medicine School of Medicine Vntiersily of Cahforninnl [,os An/telea MATT M. MIMS. M II. Assistant Clinical Professor of Sarfrry Vrologr School of Medicine Unit rrsit) of California at Las Angeles liOllEIIT O, I'EAHMAN. M.D.. F A.t S Assittiint Clinical Ptofctior of Surgery fVtologf School of Meilieine Vniterstty of California at Los Angeles IIOWAIIII I.. .STKIMIACII. M.U. Professor of Radiology NfJiooJ of Vrdtrine Cniiersiiy of California, San Francisrv CIIAKI.E.S M. .STE\*AnT, M.D. Clim'fol Professor of Uiotogj School of Medicine I'nitersily of Southern California, lots Ang'les UOllEIUCK O. TUUNF.Il, M.O.. F.\ C.S Assistant Professor of Surgery fVtohgy School of Medicine Vnitersity of California at Los Angeles EIIFSTEIl C. M INTFH. M.D Professor and Ihtcclor, Ihxision of Vrology The Ohio State Vniieriity Hospital, Coturntfus PREFACE The extraordinary progress in the field of urology during the last few years is well known to any student of our specially. It has heen my purpose in preparing this hook to cull some of the more salient advances made in the field of urologic diagnosis during recent times. No attempt has heen made to present an encyclopedic treatise on the subject; rather, an arbitrary selection has been made to collect in one book authoritative descriptions of diagnostic methods that are proving indispensable to the modern practice of urology. The diversity of subjects included in Advances in Diagnostic Urology should indicate the amazing bread!)} of our specialty. Emphasis has been placed on new uroradiograpliic techniques and interpretations; hence, chapters on angiograpliy, delayed and voiding cystourethrography, and antegrade pyelography have been included. 1 have been fortunate in obtaining tlie contributions of auUjorilies in t)ie fields of kidney biopsy, neurologic urology, prostalic carcinoma, renovascular hypertension, endocrinology, and radioisotope renography. Somewhat esoteric chapters on pho- tography and on sexual problems of men have been included because these interesting aspects of our specialty have also heen relatively inaccessible to the student. Certain technical advances have not heen included because of ibeir experimental nature or their rare clinical availability. Some other advances liave not been discussed because they are diagnostic procedures that have become ix Prefaet ({uickly atiil unhei>ally ^idoptet) and tlieir hicliiy Conrad Boenlgen, urology liocatne a truly enligliteneerg developed retrograde pyelography in 1006 after the •-eri'tulipitnii- finding of vesicnurrleral reflux at the lime of I’y-iography, IntruvciioiK urography vtas introduced in 1920 vvlien Ito'cne first vi'ualired the urinary tract after the inlravenmt* injeeiinu of sodium ioilide and urea. Von LichteiilM'rg and Swiek made thi' a safe and practical diagno'ltc pudctnlure when they ititro«lnLE RIOl'SY OF Tlin KIDNEY UO RALril GOLDMAN 7 DIAGNOSIS OF PKOSTATIC CARCINOMA m CLARENCE V. {lODCCS 8 DIAGNOSIS OF ADR ENA I. IIYPERFUNCTION W FRANK U IN MAN. JR., AND IlnnARO L.STEINBACII 9 THE RADIOISOTOPE RENOORAMi A KIDNEY FUNCTION TEST m CHESTER C. WINTER 10 RENAL PIIOTOSCANNINC IN DROLOGIC DISEASE 192 ROBERT 0. FEAR MAS 11 NEUROLOGIC UROLOGY 201 (RNEST UOR» A.ND RODERICK 0. TL’IINGK 12 ADVANCES IN C YSTO P II O T O C R A P II Y 2.M MATT M . »I I M S 13 DIAGNOSIS OF INTKRSEX PROIU.EMS 212 A \ w, INKLC Contenls xvii APPENDIXES I. OC;TtI^E OF IftSTORY AWD PHVSrCAL EXA SI I NATION IN NEUROLOGIC UROLOGY 273 Ernesl Dors and Roderick D, Turner It. RECISTEREn TRADE NASIES OF DRUGS 283 Index 285 advances in DIAGNOSTIC UROLOGY AOISTOGIi API! Y IN UKOLOGY 1 . Some of tlie original enlliubiasm for renal angiography has been tempered hy time and di'^enclianting experience. However, many of the recent advances in vascular surgery have been made possible l)y the improved methods of visualizing the renal vascular tree. Although roentgenograms of injection specimens were made as early a* 1896 (only three months after Roentgen’s dis- covery of the x-ray), it was twenty-seven years before Sicard and Foreslier’'^” used Lipiodol on living subjects for vascular delinea- tion. In 1924 Brooks, ■* using sodium iodide, popularized aor- tography in the United Stales. The main credit for the development of aortography, however, goes to a urologist, dos Santos,® who in 1929 described its nse. Between 1936 and 1942 aortography was maligned in the United Stales largely because vascular damage and death occurred in many of the canine experiments of Henline and Moore.®® In 1912 Doss" and Nelson’* revived interest in the technique, which was then used enthusiastically hy urologists for differentiating c)’sts and tumors of the kidney. Although it proved misleading and is rarely employed for this purpose today, it is still advocated for definition of adrenal and other retroperitoneal tumors (Fig. 1) Aortography is occasionally useful in determin- ing the extent of polycystic disease (Fig. 2), and it is often helpful in identifying renal anomalies such as agenesis, hypoplasia, duplication, horseshoe kidney, and ectopic kidney when other 1 Aortography in Urology 3 Figure 2. Translumbar aoriogram made by selective renal angiography, showing polycystic kidney. The ‘‘barren" appearance of the vascular tree is typical of this condition. diagnostic methods arc not adequate (Hg. 3). In hydronephrosis, renal angiography lias been recommended to determine the degree of renal atrophy and to outline obstructing vessels causing the pyelocaliectasfa. In renal trauma, aortography Itas not been widely employed, hut it sometimes aids in diagnosis when tlie patient’s condition warrants its use.^^ Both Wayde^" and Frimann* Dahl’"* consider angiography of value in localizing focal areas of renal tuberculosis and in indicating the area for partial nephrectomy. Occlusive arterial disease is now recognized as important in reversible renal iiypertension, and aortography is the definitive method of demonstrating such occlusive disease in the renal vasculature. The lesions llut produce hypertension and that can he depicted by aortography include atherosclerosis of tlie renal 4 A.DYANCCS IN DIAGNOSTIC UROLOCV Figure 3. Pelvic kidney with vascular aujipi) preoperalnely Is shoun at the left. The aortogram at the right, made after this Lidttey had been placed in the flank, shows its satisfactory susjwnsion. artery or of tlie aortn with plaque foniintion (Fig. 4), mural Itj-perplaslas (Fig. 5), thrombosis of the retial arterj’, exteriial compression of the renal vasculature, congenital coarctations, ami aneurysms. Since the techniques of aortography are now sophis' ticaled, it is usually possible to delect not only main stem arterial lesions but branch (segmental) lesions as well. UENAT. AUTEUIAI. IIEOOII SUl'Pl.Y Merklin and Michels,*’® in an exhaustive study which is iJic defuiitiic treatise on renal bIoooung woman. brandies of llie single renal artery, uliile the tcslleular or ovarian arteries are rare brandic®. Brandling of ibe main renal artery is ela>sirieil as dislributed or magislrnf. In the former tbc renal artery tUvidea into its ler* minal Iirandie*. shortly after it<» origin from the aorta; in the latter it divides near the hiliim of the kidney. In most instances the single renal arterj' divides into an anterior and posterior trunk; usually this occurs about halfway' between tbc aorta and the renal hilum or in the region of the bilum. The numher of Iin'ncipaf branches of the renal trunk varies from two In five, but most commonly there are four main brandies lliat enter the parenebyma. Three of lbe«e f the anterior sujierinr, anterior medial, and anterior inferior rami) ate derived from tbc anterior trunk Aortography in Urology 7 Figure 6, Correlalion of lermmul renal arterial brandies with segments of the kidney. and course ventrally to tlte pelvis. The fourtli main branch is a contimiation of the posterior trunk and courses posteriorly to the pelvis (Fig. 6). Graves’s studies^’ of injection corrosion casts sIjovv that the kidney is composed of five segments: apical, upper, middle, lower, and posterior (Fig. 6) . Tlie tliree terminal branches of the anterior division of the renal artery are refened to by Graves as the upper, middle, and lower segmental branches, since they supply those segments respectively. The posterior division of the artery supplies the posterior segment. The artery of the apical segment usually originates from the anterior division of the renal artery. Graves emphasized that the main branches of the renal artery can be identified arteriographically because there is a constant pattern present irrespective of the site of origin of the segmental arteries. Temporary compression of llie renal vessel, winch pro- duces a purplish discoloration of the area supplied, or injection of the vessel with Evans blue tvill indicate at operation the seg- ment of the kidney supplied by that vessel. ADVANCES IN DIAGNOSTIC unoI.OCY il TECHNIQUES OF AOnTOGIlArilY Transhtnibnr Aortography The simplest and formerly most popular inetliod of nortogra* phy, the Iranslumbar technique, was introduced by dos Santos.® It can be performed under general or spinal anesthesia, but many urologists and radiologists prefer local infiltration anesthesia. Premedication adequate to allay apprehension and to lower elc- /'igure 7. Technique of tran«lumhar aortogfaph). With the jialiont iu the prone position, the nenlle is inlroiluml four ringerhn-.'Kilhs to the left of die tuidline and just i>elow the tviidfth iih. Aortography in Urology 9 figure fi. Placement of the needle puncture in the aorta above the renal arteries. vated lilootl pressure is important. In tlie translumbar tecJmique (Figs. 7 and 8), the needle is inserted approximately four finger- hreadllis to the left of the midlinc and just below the twelfth rib, while the patient is in the prone position. Tlie needle is directed ccplialad and medially until the aorta is pierced (if the needle strikes ilic verteliral !»o’ANCES IN DIAGNOSTIC UROLOGY ihe principal advantages of the transfemoral inctliod tner the traiislumbar technique is that it allous changing the position of the patient without risk of injuring the \esscl A\uli or dislodging the catheter. We have recently hecn pcrfomiing aortography with iJie patient in the upright position ond have found that this often pro\ides hcUer delineation of the main renal arterie?, particularly nhen the kidneys are plolic."®*"'' The upriglil film in Figure 11 shoi»s a stenotic lesion of the renal artery which is not apparent in the recumbent film. It has also been of interest to learn of the possible relation of renal ptosis to the development of certain mural hyper- plasias of the renal arterj* (Fig. 12). In thin individuals 50 [icr cent contrast medium has prmed satisfactory; in heavier patients 75 per tent has been prcferahle. Wc hare seldom found it tiecc«.>*ary to use more than 20 cubic centimeters of contrast medium or more tlian 5 kilograms per square centimeter of jiressiirc for the injection. Although we were fonncrly impro'Sed witli the ease, rapidity, and cxcclicncc of radiographic definition with the transliimhar approach, we have converted almost completely to the percutaneous cathelerwalion metliod for three reasons; (1) It is safer (see Complications of Aortography, p. 25). (2) It allows greater mobility of the patient for obtaining upright films, (3) There is no periaortic hematoma, wliicli as a rule does occur after aortic puncture. Although the amount of periaortic lileediiig is seldoiii of serious clinical significance, surgical di«-«cclion may he more difncuh when llie aorta and renal aileries are explored in tlie early postaortographic i»eriod. The principal coiiiraitidiealion to the Iransremoral aortogram is aortoiliac occlusive disease. TransnxUlary /iorlogrofihy As an alternate method of placing a cnlhetcr in the aorta for renal angiography, Iransaxillar)* aortography has become popular Figure 12. Rccumlient and upright aortograms of a female patient extcnrive fibromu^cular disease of the right renal artery. Note the degree of riglit renal ptosis and improved delineation of diseased segments shown in the upright film (6efoit»). 16 A I) A N C E S IN DIAGNOSTIC UROLOGY among radtologisU.’® It con«ti>t«> of llie percutaneous puncture of the left axillary artery iimler local infiltraliou anc«tlse‘-ia. TliU arterj' is eji».ily found in the axilla when the patient’s arm U extended and his head is resting on hU left hand. A guide wire is in«erled into the axillary artery throngli an Oslo or Seldinger needle and is advanced to the aortic aich. ( Recently the of the image intensifser and television monitor ha« facilitated this mancuter.) After projver placement of llie guide wire and with- drawal of the needle, the Iwrium-impregnated j'olyelhylene luhe (similar to that u-ed in the Iransfcmornl catheterization method) is introduced over the wire and passed under lhioro«copic tcle\i- more important in this technique than in iransfeinoral caUiclcriratinn hccause of the tendency of tlie catheter to enter aortic hranches or to pas’* down the ascending aorta rather than down die de.«ceiiding aorta. Fifteen to 30 cuhic centimeters of 75 per ctml dialri/oale (Hypaque) is injected at a pressure of 5 kilograms per sijuan* centimeter, and films arc taken in rapid se<|ucnre (‘*ix frames per second for the first second and luo frames per second for eacii of llie next three -econds), Tlic tube ami ca^'-elle arc centered over the upper ahdomeii to include the kidneys and ahdoniinal aorta. This transaxilKiiy method jirovidc* angiograms of cxcellml ijualily (Fig. 4). The main indinilioii for its u-e is occlusive di** ease of the iliac arlciy, wliich makes Jransfcnioral calhclcrizaliDn diiTiciill or hazardous, h is aKo ideal for ohtaiiiing upright aorto- grams when the patient c.iii he nio^cd. Arterial complicalions from calhclerizatinii arc s.itd to Iw virtually iioncxislcnl after the traU'- axiilary procedure l»ccau*e of the rich collateral circulation and the lower incidence of alherosiderotic disp.ise in the vessels of the upper extremities than in the ahdommal aorta and the iliac and femoral arteries. Aortography in Urology 17 ScfecM're Keital Atleriography Swedisli investigators (principally Odnian**" and Edholm and Seldinger^’’) have made extensive use of selective renal arteri- ography via the femoral or brachial artery. A polyethylene catheter is employed, its distal lip being bent after it is warmed. Its curve is straightened out when a flexible stylet is introduced into the lumen. \Vlien the stylet is wilhdravm, the catheter again bends. In this technique the guide wire and catheter (with the “coude” straightened out) aie advanced into the aorta to the level of the renal artery. After the flexible guide is removed, the catheter is placed, under fluoroscopic control, with its tip toward the desired kidney and moved along tlie aortic wall. Wlien it reaches the renal artery ostium, liie coude tip of the catheter moves outside of the lateral border of the aorta, a movement easily delected fluoros* copically. A recent addition to llie diagnosis of hypertension associated with renal artery stenosis is the technique of preoperalive strain gauge manometry at the time of selective rejial arteriography. Pressures are recorded in the aorta and in the renal artery distal to the area of stenosis hy attaching the catheter to a transducer and recorder. If a gradient of 20 millimeters or more of mercury is found, the lesion seen arleriographically is probably of significance in the etiology of tlie hypertension. We have recently employed this techni([ue and agree that it has merit in the diagnosis of lesions of the first portion of the renal arteries. Renal arteriograms can l)e performed with from 5 to 10 cubic cejjlimeters of contrast medium. Jl is thus apparent Ujat ilje princiful advantage of this technique is that the artery in question can he selectively visualized with a smaller amount of contract medium and consequently with less toxicity (see Fig. 2) . One of the disadvantages of this technique is that multiple arteries to the kidney originating directly from the aorta are not visualized. Since multiple arteries occur in approximately 20 per cent of patients. 18 ADVANCES IN DIAGNOSTIC UROLOGY the risk that a pathologic process may exist in a noiivisiializcd artery is significant. Counlerciirreitt ..^orlogrflphy Castellanos and Pereiras introduced countercurrent aortography ill 1937.“ Tlicir technique consistwl of direct injection of the femoral artery ^vith contrast medium, and it depended upon the countercurrent of dye in the iliac tessels and distal aorta to o\er- come the propulsive pressure lu the aorta. This technique is of no value in urology, since dye cannot he safely injected high enough to outline the renal vessels- f/onever, a variation of ihi-* technique has heen introduced hy Karras, Cannon, and Sokol,** in wliidi the lirachial arlcr)* of the left arm is cannulaied with a No. 17 Llnnl, rouinhended needle introduced perculancously with the aid of a cutting ol*luralor. Tlie needle ib connected nith plastic tuhiug to the automatic injector. Approximately 1 cubic centimeter of 50 |>cr cent diatrizoate sodium per kilogram of body weight and an injection pressure of 8 kil* ograms per square cenliincicr are iiscil. Films, taken nitli a rapid cassette changer or Elcma*Sch6namier nnil centered over the kidney region, are started at the end of the injection and conlimicd for several seconds in onlcr to “catch” the dye ns it descends the aorta after having reached the aortic arch in a retrograde ilow through the brachial artery. Tliis technique has produced films ol excellent technical quality, hut it is tmv recent for any prediction as to its general usefulness in urology. It is commonly used in neuro- radiology to delineate the carotid and cerebral vcs«els. It< obvious advantage is that the need for catheters is eliminated. ItxirarenoHi Aorto^rophr Steinberg, Finby, and EvanN^" inlrodnced their method of rapid intravenous injection of contract medium for abdominal arteri- ography in 1959. Advocates of this method maintain that improve- ment in radiographic equipment and tiie use of rapid changers and Aortography in Urology 19 pressure iiijectioJi liave made it possible to enhance visualization of the major arteries by injection through the veins.'® Under local aneslliesia the right antecubital vein is located and a No. 9 Lehman tube is inserted through the basilic vein into tlie axillary vein or preferably into the superior vena cava. The dye can also be injected directly through a needle ivithoul recourse to venous catheterization. Tlie femoral vein or the superficial jugular vein can also lie used. Determination of circulation time is made only when tliere is evidence that it may he prolonged. Ninety-five to 100 milliliters of 70 to 75 per cent Hypa/jue warmed to 37 degrees centigrade is injected with the Gidlund automatic injector at a pressure of 4 kilograms per square centimeter. The series of films is usually started eight seconds after completion of injection; films are taken at the rate of six frames per second for the first second and two frames per second for the next three seconds, if tlie Elema- Schonander film changer is used. Witli the Sanchez-Perez Seri- ograpli, 12 exposures are made at intervals of one-half to two seconds. Usually the patient experiences a generalized flush immediately after the injection and may notice a metallic taste. Nausea, vomit- ing, headache, and convulsive seizures, which detract from the value of the technique, have heen reported. Such generalized reactions are rare when an intra-arterial loule is employed. The intravenous lechni(jue does not produce films of a quality comparable to that achieved liy direct arterial injections. Orthoalatic Renal Arteriography Kcference was made earlier in this chapter to upright aortogra- phy. This melliod was recently introduced to aid in the diagnosis of stenotic lesions of the renal arteries associated with hypertension. Arteriograms in the erect position may he made by three tech- niques: tlie percutaneous transfcmonil method, the percutaneous Iransaxillary' method, and the translumhar aortic puncture 20 AD^ANCES IN DIACNOSTIC UROLOGY approach. We Jia^e employed the Eleina-Sclionaiuler unit wliirfi can he rotated 90 deprees-, alloM'ing the patient to stand during: the test. It is possible to perform the test !>)• the Iraiislnmhar mclliixl using a single him \wfli the patient prone and seniiiipn'ght on the cy«loscopic table. The JiCst of these aj>proaches is prohjhiy the tran«fcmoral. The catheter is placed In the aorta with its lip at the upper border of the second lumbar vcrlehnil body. After filin' in die rccuniijenl position arc made, the catheter js taped to tlic thigh, and the patient is assisted off the table, exercising niodcMle cau- tion to keep the leg extended. He then asstmies an erect posiiion at the Elema unit, the catheter i«. coiineeled to the Gidlund injector, and a second series of films is made. Tlie transaxlllary technique a]loi\.s easier movement ol the pa- tient, hut it is a nioic difficult procedure than the lran*fcniorat nni] requires the use of the image-inlcnsilying screen. Tliendore. for the majority of patienN the transfemornl method is the preferml one, It is possilile to obtain diffeienlial strain gauge manometry U‘>iiig the selective catheterization lccl)ni(|uc and then to lea\e the catheter in the aorta to obtain erect films. There are several advantages of orlho-lntic renal arteriography. The renal arteries are better delineated than in eoinenlinnal lech- niijucs. In the upright po'-ition the kidney usually dcscciuN and places (he renal artery on stretch. Tortuosity i< eliminated to a great extent, and areas of nurroning or dilatation are belter '>l•en. In addition, there i« los filling of other \es..els which freijuently oxerlip and oli«cure the renal arteries. Figure 1.3// shows a stenotic lesion in the fir^t third of the right renal artery and oierliing «-pknic artery opacihcAlion making a definite stntvnw’wt of the condition of the left renal artery impossilde. The ortho-talic arte- riogram (Fig, ir-1/7) discloses a marked degree of renal plo‘i< on both side«, hut particiil.'trly cridciit on the right. In addition, with tlic left renal artery placed on ilretch and in the ah'ence of oier- lying splenic artery filling, it is app.irent that the left renal ailcrj' is normal. Figure 13. (yl) ilecumlieiu arteriogram ehowing a stenotic lesion in the first tfiircl of the right renal artery. Tortuosity of the left renal artery and overiving splenic artery opacification obscure the condition of that vessel. (li) Erect arteriogram discloses a marked degree of renal ptosis on both sides, but particularly on the right. In addition, A«lth the left renal artery placed on stretch, it is apparent that the left renal artery is normal. 22 ADVANCES IN DIAGNOSTIC UROLOGY Because of the frequenl associalion of stcnolic lesion^ of the renal arteries and nepliroplosK, it is po-silile that exces-'lve niohil- ity of the kidney may be respon-ible for the development of inur.iI hyperplasias in some cases. COMTLtCATIONJJ OF A O U TO G ll A I’ It Y Smith”® has reported no mortality or serious morbidity in over 1500 cases of transliimhar aorlogra[iliy. However, a variety of complications with tlie use of the various icchniqii('& has hern reported sporadically. A’ ephroloxicUy The ideal contrast medium is one of high opaeirication and toxicity. Sodium iodide ami thorium dioxide were soon abanduntx] following reports of signincant mortality and morliidity. In addi* tion, sodium iodide was often painful and tliorium dioxide pro* duced late complications because of its radioactivity, lodopyrucet and dtalrizoate sodium have proved much safer. Urokon possesses the most iodine per vinit weight of any of the newer contrast media and provide^ vascular opaciftcaliou of greater intensity than that obtainable by any other organic iodide angio- graphic contrast sohitioii,"* Vcl, from data presented liy Killen anotciilial for v.i'-cnhir opaeificalioii, it is less toxic. Fifty per cent Hyjvaquc is often suffirient for thin individuals, hut 70 to 75 {ver cent provides belter contract without significantly increasing loxirily. The solution should lie warninl to body temperature, ami llic amount injected .shonhl Ik* limited Aortography in Urology 23 to the smallest volume llial will provide good angiographic definition. Nephrotoxicity probably occurs to some degree in all aortog- raphy; manifestations may range from albuminuria and micro- scopic liematuria to serious elevations of the blood urea nitrogen, oliguria, or anuria. In reviewing 12 cases in which death resulted from renal damage, McAfee"* slates tliat tlie patients died as a result of uremia 12 hours to 13 days after aortography. Renal damage following aortography is probably glomerular as well as tubular, as shown by Idborlm and Berg.®* Various studies of the nephrotoxicity of organic iodine compounds injected arterially reveal that the severity of the renal complications is directly related to the amount and concentration of the contrast medium, with Urokon being one of tlie most toxic sulistances and Hypaque the least toxic. Recently Conray has been introduced and promises to Ije an excellent and safe angiographic medium. Luttwak, Reed, and Breed"® have shown tltal, in aortography performed either above or below the renal vessels, injection of one per cent procaine just before injection of Urokon results in a somewhat larger effective renal plasma flow than when procaine is not used. Pre-existing renal disease may he important in the production of renal damage by aortography. I have seen two cases of anuria occurring three and five days after aortography had I)een per- formed in the presence of a solitary kidney. I am also aware of one death that occurred in a similar situation. It is now thought tliat adequate hydration of the patient before the procedure serves as a renal safeguard and that mannitol used as a diuretic before and after aortography may obviate some of the toxicity. Certainly the rapid infusion of 1000 cubic centimeters of 5 per cent ghico'e in water, as ad^’ocaled by Beall," is of value. At the University of California Hospital in Los Angeles, aortog- raphy is usually performed under local anesthesia so that the patient can lake oral fluids the same day. 2t ADVANCES IN D f A C N O S T I C II n 0 L O C Y A’euro^ogtr Coriiplicntions Tlie neurologic complications wliicli )i.i%e been reported range from minor problems such as Iramicnt pAre>lbe«ii\ to trans\crse myelitis ami permanent paraplegia,’ “ Death has occurred in several instances, usually as a result of pneuni *iiia or other com* plications of tlie paraplegia. Neurologic riamage to the '■pinal cord is apparently CHinsed liy direct lotic action of the contrast niediiini on the cord, which receives its major blood «upplj from the radicular arteries and the anterior spinal arlene*-. There have abo been several instance', reported of puncture of the suharachnoid space Ijj the aortograpli} netHlIe. Mo^l of the repoiled neurologic complications have occurred, however, when the needle had ht>en properly placed in the aorta ami there was no direct trauma to the spinal cnid. It has been claimed lliat aortic eomprc"«ion or aortic occlusion distal to the major radicular arterv’ U'uallv arising from the left lumbar artery U a predi«posiug cau*c.^'' The incidence of neurologic complications np|)ear'» definitely to be higher after traii'Inmhar aortography ih.in after u-e of the traiisfemoral [iroccdure. J’airiilnr Ctfiniiticationf Secondar)' to transfcmonil aortography (callieteri/alion), it is not iincoinnion to find a cold, Idue extremity lasting for several minutes following the withdrawal of the polyeihvlene catheter from the femoral artery and at the time that pre"\ire is applied to the puncture area to control Iilmling. Accidents have heeii reported in wliiili the polyethylene catheter was slicared ofTliy llieitcetllc when the catheter was withdrawn with the 'liarp beveled needle in place. With the iwe of the Schlinger needle and the introduction of the catheter over fiexible wire, tin* compUcalton, although not enlirelj ohvtated, ha« heen ininimi/ed." EmhoIi*iii following aortography ha', heen reported ami has re* Aortography in Urology 25 suited eillier from dislodgment of an atheromatous plaque or from delayed propagation of a tlirombus originating at the punc- ture site/ Intramural injection of contrast medium has been witnessed by most urologists performing Iratislumbar aortography. This can happen as a result of the gradual lifting of the needle by the periaortic hematoma after ideal initial placement of the needle. This occurrence is usually not of serious import. Aortic dissection, however, is a potential complication of intramural injection of the medium, and dissecting aneurysm of the aorta as well as mesenteric occlusion liave been reported.^' Although such vascular compli- cations me prevented by the peripheral arterial catheterization melliods, other iiazards aie piesenl in aortography. We recently saw a patient who had a severe hemorrhage into the tliigh four days after a “simple” pei-culoneous puncture and catheterization of the femoral artery. Tliis condition required fenjoral arterior- rhaphy. We liave also learned of a similar complication occurring four weeks after tiansfemoral callielerization."* McAfee”^ found 5 local complications in 375 cases of transfeinoral aortography, including perforation of the arterial wall by tlie catheter, a post- traumatic arteriovenous fistula, an instance of shearing of the catiieter tip resulting in emlmlization and consequent amputation of the extremity, and formation of large hematomas. We have seen two shearing accidents requiring arteriolomy and extraction of t}je catheter fragment from the leg. With the Seldinger method, formation of Iiematomas is rare because the catheter is introduced over iJie smaller wire and creates a “tight fit” in the puncture hole. A hematoma may occur after the catheter has been removed, but pressure over the puncture site for ten minutes followed by a pres- sure dressing is usually an excellent safeguard against this sequela. Arfonad administered by intravenous drip during the procedure, as advocated by Poiilasse,'’'* minimizes the formation of hematomas iiv patients wlio are severely hypertensive. 26 ADVANCES IN DIAGNOSTIC UROLOGY Gastrointestinal Com plication* Although ill the early years of aortography mesenteric lliromiMi- sis was reported in several instances after flie use of 80 per cent sodium iodide, gastrointestinal complications have, since t)ic advent of less toxic contrail media, hecome ver)’ infrequent. Among some of the rare accidents reported are: pancre.\tic necro- sis following excessive injection of tlie medium into the celiac axi^; infarction of the descending colon from overinjection of the medium into tlie inferior mesenteric artery; and severe pain or infarction of the ileum or small Lovvcl from injecting the contrast material into the superior mesenteric artery.’' Such complica- tions are more likely to occur when the aorta is ohslructed hy dis- ease or hy compression distal to the injection site, and vvhen excessive quantities of dye arc introduced directly into or near these branches. Another complication of aortograph> is allergic reaction to the contrast medium. However, f1u«hing, nausea, vomiting, and sjm- cope occur less frequently after intra-arterial injection than when the contrast medium has licen introduced intravenously. I'REVr.NTION OF COMPLICATIONS Proper placement of the needle or callieter is of prime itnpor- tanco. Injection of a safe conlraM medium (50 to 75 per cent diatrizoate. sodium, or Conray) at pressures and (juanlilie< which are adequate but not excessive, also results in fewer complications. Tlie iransfenioral or lran«hracljjal mcthoed overnight after any type of aortography. Because delayed bleeding remains a possibility for several days, patients should be cautioned against strenuous activity during this time. Aorlograpljy in urology is a diagnostic method that has w’axed, waned, and waxed again, and is now an accepted, safe, and widely used procedure. Angiography in (he diagnosis of renal tuberculosis, trauma, hydronephrosis, renal anomalies, and adrenal tumors is a valuable adjunct to other well-establiriiod urologic techniques. Its primary application at this time, however, is in the definition of ADVANCES IN UIACNOSTIC USIOLOC^ 2 « llie renovascular pattern, with particular icference to llie detection of stenotic lesions of the vessels and to the identification of area* of segmental ischemia. nKFRWnNCKS 1. Ahesliouse, P. S., and Tionpeon, A. T. Parajdrgia: A rare coiDpIica- tion of translutnliar aortugrapli). J. Urol- 75:.lt8, 195f». 2. Beall. A. C.. Crawford, E. Cou\c^, C. M., DeBakej. M. E., and I\Jo)er, J. If. Complications of aorloprapli) : Factors influcncitip renal function following aortography with 70'« I’rnUon. .‘'urper) 13; 3f>t, 1938. 3. Biryarsk), S. Paraplegia following trori«Iuinl«ar norlograplij. /.d.lf.d. lSfi:S09. 1951. 1. Brook*, n, Intta>artcriat liijerllun of sodium iodide: Prrliminan report. J.AMJ. 82:l01f.. 1921. 5. CaMellanoi, A., and Pereira*, ll. lirtrograde nr coiniter-turrenl aorlograph). Am. ). Hoempenol. r»3:.5r>9. iy.>n. 6. Cope, C. Intraranular hreakape «*f Seldiiiper •pring guide wire*. J.AMA. Jfi0:10r.l, 1962. 7. Craw-ford, C. S.. Beall, A. (^. .M»f>cr. J. 11.. and Delkikew M. Complication* of nortograpliy. 5Mrg. Cjnec. & Obst. 10l;129. 1957. 8. Po«s, A. K., Tliomas, II. C., and Bond, T. B, Benal nrtrriopraplo: In clinical >alue. Texas J. .Vcd. 38:277, 1912. 9. Dos Santo*, R., I.ama«. A., and fVrcIra Culde«, J L’artenoprsphie (les mcmlires nlraeriencrs nilh translumhar aortograiili). ITesl. }. Surg. 6fl;309, I960, 37. Stciiilierg. I., Finhy. N.. and Evans J, A. A safe anti prarlkal method for abdominal aortography, peripheral arterlographv, and angiography. Am. J. fioenlgenot. (12:7.3(5. 1959. 3fl. Suh, T. II., and Alexander, L. Vascular system of the hum.in spinal cord. Arch. Seural. Psychiat. U:659. 1939. .39. Wagner, F. H., Jr., Price, A. If., ami Svienson, P. C Al-dominal arteriography : Technique and diagnostic application. Am. }. Roent- genol 5a:591, 1917. Aortography in Urology 31 40. Walter, R. C, and Goodwn, W. E. Aortographj and retroperitoneal oxygen in urological diagnosis: Comparison of translumljar and per- cutaneous femoral methods of aortography. /. Urol. 70:526, 1953. 41. Walter, U. C., and Goodwin, W. E. Aortography and pneumography in children. J. Urol. 77:323, 1957. 42. Wayde, U. Abdominal aortography in renal diseases: Preliminary report. Bril. J. Radiol. 25:353, 1952. 2. CYSTOGRAPHY AND VESICOURETERAL REFLUX CHARLES M . STEWART TUn DKI^AYED AND VOIDING CYSTOCIIAM Delayed imd voiding cyslograni U a eleecriplivc name for a recent variant of cy?togra|>liic proceilnrc. Since tlic initial ri*iM)rl of tins terlmifiuc in 1951, it lia« completely dunged llie palliologtc* pliysiolog'ic cnjicepl* of vesicoureteral reflux and efUiix. TliU tech- nique is now uni>ersally accepted a- the niO'l dependahle method for obtaining a pcnnancnl visual record of the heretofore \mhnown physiologic caprice of the \c«icourolcral junction. The discovery of the \alue of the technique was serciidipitou*. Early in 1918 aJi accidental change hi our usual cystograpliic routine proilueed sonic unusual rcsulK Contrast medium had hecn instilled into the Madder of an adult female suffering from a con- tracture of the Madder nech. Tlie patient mcned iluring exposure of the fdm and the technician was adiised to repeal llie cx|>osure. Approximately 30 mhmtcs clap«e«l lipforc the second film taken, however, and then a lliiixl expo-urc wii" taken after another 30 minute-, because it was liclicved that the second had been under- exposed. Thu-- inadrcrtently the first one-hour delu)ed cvstogratii was recorded." ■* Tlie first film repealed the typical, iralieculatcJ outline of a ehroiiically olistrucicd Madder; the .HO-miiiute olxlrucl bladder outlet. iVeurologic eongenilal Deformities of spine and spinal coni or roverinps r»-sull in nerve root damage and derange Tiormal plijsiolog) «>( vixirouirternl junction. AVuro/ogic acquired Interruption of nerve pallwavs at cord level or at roots of raiida eijoini by lesion; an) trauma to ncuraxi*. Cystography and Vesicoureteral Reflux 35 Nonneurologic acquired Bladder neck obstruction: (1) benign prostatic b) perlrophy, (2) bladder neck contracture, (3) carcinoma of prostate. Urethral stricture: (1) traumatic, (2) inflammatory. Mental stricture: (1) traumatic, (2) in- flammatory. Heimjilantation of ureters into bladder. Ureteral stump following nephrectomy. Surgical trauma to ureteral orifice. Cerebral concussion Transitory, ending with reco\ery from concussion. TECHNIQUE OF CYSTOGRAPHY In most instances cystograpliic studies should not be delegated to a technician or to a radiology department. Optimum informa- tion is best obtained wlten the entire study is performed or closely supervised hy llie urologist. Cystography under general anesthesia should he avoided as unttccessary and possibly misleading. Bunge' has observed that some patients will) known bilateral ureteral reflux occurring during cystograpliic study without anestliesia failed to reflux when tiie study was repealed with spinal anesthesia. Slightly warmed contrast medium is slowly instilled through a catiieter by means of a piston or bulb syringe. The bladder need not be overdistended, for reflux may occur with the bladder only partially filled. It has been proved that reflux is no more likely to occur from a completely distended or overdistended bladder than from a bladder which is only partially di'^lendcd. Tlie amount of medium instilled will vary and must be estimated according to llie patient’s age and ability to cooperate and to the degree of vesical irritability. One to four ounces are usually sufficient for infants and children; the quantity necessary for the average adult may vary from four to ten ounces. Best results are obtained when the bladder is filled only to a degree compatible with comfort. For children and adult females of nervous temperament a local urethral anestlietic may lie used. Urethral anesthesia partially 36 ADVANCES IK DIAGNOSTIC UROLOGY masks llie sensation of urgeiicj* Mhich may resoll from the pa-sage of the callieter, and dcLTeases the sliglil irrilaliou occusloiull) caused hy cystograpliic contrast media. Of four types of contrast mediums ^^llich I have u-al during the past 13 years, I have found tiuit diacetrizoale (Urokon) causes the least degree of urgenc}* when retained in the bladder for inter- vals as long as two to three hours. Diacetrizoale mu-t he U'^ed in concenlraliou of no less than 18 to 20 per cent. Only this con- centration will detect iiegiiining reflux in patients in whmn the tnedium might he diluted as it enters a markedly dilated ureter. In ihosc portions of the upper tract in which incomplete reflux filling occurs, clear definition is uncertain when a contrast medium of less concentration is used. In infants and children loo young or loo ill to civopcratc, instillation must he made through an inflated 5 cubic centimeter Foley catlieler of sm.ill callher. Hetenlion of the contra«t medium can then he maintained by a catheter clamp for any time interval desired."' The first film is taken immediately after the in-lillalion of the medium; sulisecpicnl fiUw> arc taken at 15 to 20 minute intervali thereafter. Hcflux may Iw dela)ed in some patients ns long as two and one-half to three hours, or it may occur after one Interval and disappear after a later interval. Each film should therefore If developed and viewed imiiKHli.ileIy. Time intervals and variations in angle of exjio-tirc may then he changed when iii'ce— ary to sup- plement the immediate finding-.*'* " Figure ] sliows the dilated Idadder of chronic Madder iKark uh-tnutiun and hilateral ve-i- roureteral reflux. The ililaUxl jtelvi- on the left h.id not been evWtTiY in rfftnocrioo- -int»gT»tJlrrf. Voiding cj-stourcterographic films are u-ually taken at the termination of a delated cystograpliic study. However, forceful voiding stuiHes may n!-o l»e made initially, immeill.'ilely after the iii-lillation of contra-l nit'diuni. Films taken promptly after force- ful voiding are ino«t ca«ily oirtainrd when the patient I* in an Cystography and f'esicoureleral Reflux 37 Figure ], Cystogram sliotving bladder associated ivitli cJironie bladder neck obstruction and bilateral vesicoureteral reflux, Tbc dilated pelvis on the left had not been evident in intravenous urography. erect position on an upright table. Male diildren may void directly into a container held by an assistant, females into a roll of towels placed high between the thighs. A commode devi«ed by Dr. Robert Peatman has a lial“a wood seat and a plastic container. This allows the female patient to sit and void in Juxtaposition to the upriglil radiographic table (Fig. 2). The first film is taken while the patient is voiding as forcibly as possible; tiie second film is exposed immediately upon the com- pletion of voiding; and the third and final film is taken five minutes after voiding. Tlie second exposure will record the presence or ADVANCES IN DIAGNOSTIC UnOLOCY 3{i Figure 2. Pcarman commwJe u<>«t] in female c)8lograpli). oh^ciirc of rt-sidual urtiic in tlic lilaildrr and nil! aUn (Ictiio>tt>trntc llie voltinic of inediuni refluxccl iiilo llie iipprr iracl during voiding. The llilrd film will dcmon-lratc llic relciUlon of refluxed mnlium by the upper iruci, if it occur-*. Tlie final film will al-o -how llic amount of refluxed iipjHT tract iv-idual urine after it fia-i cfllutetl hack into the Madder. If an infant or child is loo young to coojierate, the hl.ufder may he slightly o\crrilled and the catheter immediately removed. With the patient supine or partially erect, a film is expo>ee5icoiireteral reflux showed a startling disparity Ijelwcen the appearance of the upjK-r urinarj' tract recorded by intravenous urograms and that demon* slrated by ejstograpliic study (Fig. 1). iMaximal ureteral and renal dilatation is often indicated by cystography x\hen that shown in the patient’s coinjiaralive intra* venous and retrograde studies is v»itbin the normal limits. I believe ibat these nonnal recordings are achieved because intravenous urography is done in the ab'*encc of the coinlitious knov»n to Ik* conducive to reihix. The hl.idder is at re-t and iheoielically cmjily at the start of an intruvenons iirograpliic serie». Henul output js necessarily low boiunU'C of deliberate dcliydration of the patient. The entire series is usually fiiudied in 12 to .30 minutes, winch precludes excretion of enough urine for reflux to occur. Ilellu'i may orcur (luring the micluriiton terminating an tniravc' nous urographic series, but the fdrn uiu^l be exposed ju**! at the end of voiding if 'tich reflux to !«.* proved by llie roenlgeiio* gram.” Iletrograde pyelography is al*o performed in the ab'ctice of conditions known to incite reflux. The bladder usually is emptied after the ureteral calheters have licen iiitro«liiccd and hefore the cystoscojH* sheath i** rcinowvl. !*yeh»granv'» and ureterogram*' are obtained after the contni'-l medium ha' been injected with a retrograde pre"ure usually not exewding that exerted by gravit). Ureteral caibcfer' are foreign IkmIics, and nllbougli the Irniima of retrograde cathclerizattun i' minima!, the pri^'cnce of catheter* within the Imiieii stiinuhiles the urrierul v%alls to coii'lrirt and tliereiiy inhibits reflux. Setjnenrr of IUafnn$llr .f/rf/im/« Tlie sequence of studies in urologie diagnosiH is import.int. When congenital bladder neck oh'inieiion i« a pi)''diililv. the initial diagnostic procedures should l«* delavetl and \(«iibnp cv-'tograms. The voiding irv'logram will often show the collar Cystography and I’esicotircleral Reflux 41 :onstriclioii at the bladder neck and the po'tateiiolic urethral iilatation (see Fig. 9, Chap. 4). It is not uncommon that delayed and voiding cj'stograms of a child wlio^e intravenous urograms and retrograde pyelograms are normal ie\eal advanced uretero- renal deterioration. Often the information obtained by cystog- raphy is diagnostically complete, making unnece-ar>- further roenlgenographic investigation."* If cystography demonstrates icHux on one side only, it is manda- tory that intravenous urograms and/'or letiograde pyelograms he performed to estahlisli the functional status of the kidney on the opposite side. A final diagnostic check, utetliiocystoscopy, is performed to verify tl.e information ohtained hy cystographv and any pathology impossible to demonstrate cystogiap lica y. Bladder A’ccfc Obstruction If bladder outlet olistruclion is suspected, the entire circum- ference of the uretlira and bladder neck shouhl he visualized with the direct vision urethrocystoscope." » Visual inspection should start at a point slightly proximal to the spinneter. Ohstmclivc lesions are most evident if urethroscopy is started when the Iiladder is empty. Tlie bladder outlet should lie kept under continuous vision as irrigation Iluid is slowly permitted to fiow into the bladder. , i c •. The child with proved residual urine will present a deamte visilile obstruction when the bladder is emplj. ic o slruction will remain obvious until the bladder becomes disten e to a degree greater than Urn amount of known Iiladder retention. For example, in a cliild witlt 60 cnhic centimeters of residual urine, an olivions ohstraction will he visible until bladder d.stent.on ex- ceeds 60 cubic centimeters, tlic known amount of retained urine. As tlio amount of fiitid in the bladder increases beyond 60 cubic centimeters, die collar or semicollar ol obstructive tissue will he seen to iron out slowly and eventually disappear. 42 advances in diagnostic UnOLOCY Finally, after llie bladder is distended, tlie outlet siiould be ob«en'ed as tlie bladder content is permitted to flow back out through an open stopcock. As the decreasing amount of bladder content approaches 60 cubic centimeters and as the bladder and the collar of obstructing tissue contract, the obstnictue lesion will be ohser\’ed slowly to reappear. Obstruction is complete when the bladder has contracted to a point past which further evacuation of the remaining bladder content Ifecomes impossible.^^' Gaping “golf hole’* ureteral orifices, which were visualhed cystoscopically during the initial investigations, have not been proicd necessarily diagnostic of vesicouieteral reflux. On the other liand, ureteral orifices arc judged competent on cystoscopic ex' amination if they exliibit normal contraction-relaxation motion in response to ureteral peristalsis. Efflux of urine does not c.ause the orifices to gape. Careful observation reveals no physiologic abnor* mality. Yet cyslographtc study may demonstrate incompetence with gross reflux. I believe tliat 95 per cent of the children suffering from xesi* coureleral incompetence with reflux have some degree of bladder neck obstruction, and that the severity of the reflux and of the sec- ondaiy upper lr.act dilatation is directly proportional to tlie degree of ohstruclion and to the length of time that the ohslniction has existed. The remaining 5 per cent of the children with demonstrable reflux probably have minor neurogenic or mechanical obstructions. Al present we lack the diagnostic capacity to recognize and cate- gorize tlie factors initialing the condition in ibis group. These children do not have a v'isIbJe amount of outlet ohstruclion; the bladder wall may vary in thickness from thin to normal. Trabec- ulalion is not .«cen during cystoscopy nor is it demonstrable by cystography. Cystography and Vesicoureteral Reflux 43 REFERENCES 1. Dunge, R. G. Personal communication, October, 1957. 2. Bunge, R. G. Personal communication, December, 1961. 3. Stewart, C. M. Delayed cystograms: A new aid in urograpluc diag- nosis. Urologists’ Correspondence Club Newsletter, Sept. 28, 1951. 4. Stewart, C. M. Delayed cystograms. £/ro/ 70:588, 1953. 5. Stewart, C. M. Delayed cystography: Supplemental report. Urolo- gists’ Correspondence Club Neivsleller, July 29, 1954. 6. Stewart, C. M. Delayed cystography and voiding cy sto-ureterog- raphy. J. Vrol 74:751, 1955. 7. Stewart, C. M. Comments on surgical lersus conservative manage- ment of vesico-ureteral reflux in children without demonstrable bladder neck obstruction. UroJogi«ts’ Correspondence Club News- letter, August 10, 1956. 8. Stewart, C. M. Discussion of: “The Standard Columbia University Cystogram” by J. K. Lallimer. Presented at 52nd Annual Meeting Am. Urol. Assoc., Pittsburgh, May 6-9, 1957. 9. Stewart, C. M. Reflux, \esico-ureleral: Comments on management and criticism of attempts to standardize cystographic diagnostic techniques. Urologists’ Correspondence Club Newsletter, October 10, 1957. 10. Stewart, C. M. Present status ot diagnosis and treatment of vesico- ureteral reflux. Urologists* Correspondence Club Newsletter, October 8, 1958. 11. Stewart, C. M. A new infant cjsto-uretliroscope. /. Urol. 81;800, 1959. 12. Stewart, C. M. Is it logical to instruct patients with vesico-ureteral reflux to practice double or multiple voiding? Urologists’ Correspond- ence Club Newsletter, January 4, 1960. 13. Stewart, C. M. Congenital bladder neck obstruction: Diagnosis by delayed and voiding cystt^raphy and surgical removal by use of a new cold, crush cutting punch. J. Vrol. 83:679, 1960. 14. Stewart, C. M. Panel on ureteral reflux. /. Urol. 85:119, 1901. 3 . PE It CUTANEOUS A N T E G It A D E PYELOGRAPHY W I L L A II 1) K . G O O D W J X Tlie lerm nntegrade p)'clograpliy ua^ first used by D. M. Davis ill 1953 to describe ibe procedure for securing a pyeloureterogram after injection of a iiydroiieplirotic renal pelvis ivitb radiopaque material. Tbe teclmu|ue and hi'^torica! aspects of this procedure have been described by Ca«ey and Goodwin.^ I N D f <: A T I O X S Percutaneous antegrade pyelography has di'-tinct value in hydro- nephrosis and ureteral obstruction when tbe point of ureteral obstruction or tbe cause of hydronephrosis cannot be ilemonslrated by conventional intravenous or retrograde pyelography. It ma) also have some usefulness in bilateral congenital hydronephrosis ulien an infant is too small or too frail to willislaiid cystoscopic manipulation. Although essentially innocuous, antegrade pyelog- raphy should not be attempted in patients in uliom diagnosis can be adequately established by conventional urologic procedures nor in patients with bleeding tendeiicie--. 14 Percutaneous Antegrade Pyelography 45 TECHNIQUE Needle puncture of the renal pelvis is not difficult in patients witli large hydronephroses, hut it liecomes increasingly difficult in cases of smaller hydronephroses. The procedure probably should Figure 1. Technique of {lercutaMeoUi* antegrade pyelography. TJie needle may he introduced v\ith the patient lying on his foce on a radiographic table. Radiographic control may he used if desired. The usual point of puncture is where a thirteenth rib would he and approximately four to five fingerhreadths lateral to the midtine on the side of the suspected hydro- nephrosis. (All illustrations arc reprinted from The Journal oj Urology, courtesy of The Williams &. Wilkins Company, Baltimore, hfd.*) 46 ADV'ANCES IN DIAGNOSTIC UROLOGY F igure 2. Sagittal section sliouing relation of needle to kidney. Note that no nlal structure lies l>elneen the lumbar skin and the renal pelvis. be reser\'ed for patients who have kttown or suspected hydro- nephroses exceeding volumes of 20 to 30 cubic centimeters and in whom diagnosis either is incomplete or cannot he made hy conventional means. Scout films, cystograms, and excretory atid retrograde urograms should he made or attempted before antegrade pyelography is Percutaneous Antegrade Pyelography 47 performed, except in the case of small infants with suspected hydroneplirosis, in whom retrograde pyelography may be con- traindicated or didicull. Preliminary films delineate renal size, shape, and position and are essential to the correct performance of the procedure. Figures 1, 2, and 3 demonstrate anatomic relation- ships important to antegrade pyelography. Figure 2 shows that the hydronephrolic kidney lies in the renal fossa and that there is no vital structure between the renal pelvis and the lumbar skin. A skin marker may be used to locate tlje approximate position of the renal pelvis in relation to the tip of the twelfth rib and the lumbar vertebrae. The patient sits or lies pione on a radio- graphic table during the procedure, and infants have sometimes been held in the arms of the nurse or mother. tigure 3. Cross-sectional anatomy involved in antegrade pjelograpliy. ADVANCES IN DIAGNOSTIC UROLOGY After local atiestlicsia and meticuiouis cleansing of tlie skin, a 5* or 6-incli, 19- or 20-gauge spinal needle is introduced through the lumbar area into the renal pelvis. The procedure is not painful. Usually urine is obtained by aspiration after tlie needle passes through the lumbodorsal fascia and into the soft portion of the kidney. In adults urine is usually aspirated at a depth of 4 to 5 indies. A specimen is collected for culture and microscopic study. If the patient has been given intravenous indigo carmine before the procedure, the blue dye may appear in tlie aspirated fluid and establish it as urine. After pelvic puncture 15 to 20 cubic centimeters of urine are aspirated from the liydronephrolic pelvis before injection of the contrast medium, either Skiodan or Hypaque, ivith a syringe. If a large hydronephrosis is piesent, more mine may be aspi- lated and proportionately more contrast material may he in* jected. Usually 5 to 10 cubic centimeters of 40 per cent contrast material is ade(iuate to obtain excellent pyeloureterograms. It is important not to o^erdistend the renal iielvis. The amount of opaque material infected should always be less than the quaniUy of urine aspirated. After the opaque material has been injected and mixed by barbotage, tlie needle is usually witlidtattn. Preliminary films may be made Nvilh the needle in place to demonstrate its position in relation to the kidney and the liydronephioais. When the needle is \dthdcawn, the site of the puncture requires no attention. Radiographic films are exposed with the patient in hotli prone and supine positions; upright films may aUo be helpful. Emptying of the pelvis and ureter may be sludietl hy films exposed at hourly mtetvaVs. In some insUmces the absorption of the iniecteil radi* opaque material hj llie Iiydioneplirotic kidney has led to excretion Ity the contralateral kidney. Percutaneous Antegrade Pyelography 49 nnsuLTS We liave used antegrade pyelograpliy frequently in the last ten years and have encountered no serious complications. Some patients develop a cystoscopic-like reaction after the procedure, hut this has usually been related to overdistenlion of the renal pelvis with opaque material. The procedure is of inestimable value in patients who have a severe obstructive hydronephrosis which cannot be adequately demonstrated by retrograde pyelography and in patients in whom renal function is too poor for the excretory system to he visualized by conventional intravenous urography. Hydronephroses of various types have been well delineated by tills procedure. In many instances ibe point of ob'-truction has been accurately demonstrated (Figs. 4 and 5). Antegrade pyelog- raphy has also been used to determine whether patients with hydronephrosis after ureterosigmoidostomy have obstruction due to urelerosigmoid stricture or whether the hydronephrosis is due to reflux (Fig. 6). The procedure lias l>ee« especially helpful in children and infants having large hydronephroses with indeter- minate points of obstruction, when It is important to discover if the obstruction is at the ureleropelvic junction, at the ureterovesical junction, or at tlie bladder neck. The quality of the roentgenograms has generally been excellent. We have come to look upon this procedure as routine when the correct interpretation of the cause of unexplained hydronephrosis is not available by other means. A natural outgrowth of antegrade pyelography has been per- cutaneous trocar (needle) nephrostomy, used for intermittent or continuous draining of hydronephrosis." Although we continue to use it in selected cases, this procedure is not as useful as we had originally thought; for once the trocar has been introduced and the polyethylene tubing has been passed into the kidney pelvis Percutaneous Antegrade Pyelography 53 for drainage, the surgeon may lie committed to further surgery. If any stoppage or obstruction of the tubing occurs, it is necessary and important to operate immediately. Nonetheless, in certain cases percutaneous needle nephrostomy has been of great value and should continue to he used in patients needing continuous drainage of a large hydronephrosis before definitive surgery. The procedure of trocar nephrostomy in hydronephrosis should not be considered a definitive operation. UErnnr.NCES 1. Casey, W. C., and Goodwin, W, C. Percutaneous antegrade p)elog- raphy and hydronephrosis. ]. Urol. 74:164, 1955. 2. Goodwin, W. E., Casey, W. C., and Woolf, W. Percutaneous trocar (needle) nephrostomy in hydronephrosis. J.A.M.A. 157:891, 1955. 4. OTHER ADVANCES IN UROLOGIC RADIOLOGY JOSEPH J. KAUFMAN ABDOMINAL VENOGRAPHY Dos SaiiJos^ in 1935 described a metliod of visualizing die inferior vena cava roentgenograplncally by iiijecling concentraled Diodrast into the surgically exposed saphenous vein. This tech- nique received no particular attention until 1947 when Farinas® and O’LaugliUn^^ independently described their techniques for roentgen visualization of the inferior vena cava. Farinas can- uulaled the saphenous vein in the thigli after surgical exposure, whereas OXaughlin departed from surgical methods and per- formed percutaneous puncture of the femoral vein unilaterally. In 1950 Stable*^ reported bilateral percutaneous puncture of the femoral vein with IG-gauge needles and injection of 60 cubic centimeters of 50 per cent Diodrast. In 1956 we reported several techniques of abdominal venogiaphy and demonstrated their value in urologic diagnosis.*^’ Although abdominal venography has a limited sphere of ap- plication, it may nonelheless be of inestimable value in demonstrat- ing caval and pericaval pathology. Because complete or incomplete obstruction of the inferior vena cava commonly causes no clinical signs or symptoms, the diagnosis of such conditions is rarely made outside of the operating or autopsy room. It is to fill lliis hiatus in diagnosis that abdominal venography is needed. 51 Other Advances in Vrologic Radiology 35 Abdominal venography can be useful to determine the presence of intrinsic obstruction of tlie inferior vena cava by blood clot or tumor thrombus; to determine the presence of partial or complete vena caval block by extrinsic pressure caused by abdominal and retroperitoneal tumors or by pericaval lymph node enlargements; to outline retroperitoneal tumors for surgical treatment or roentgen therapy; and to outline caval and renal or ureteral anomalies. Because renal and adrenal tumors may involve the vena cava by direct venous extension of tumor thrombus or by external com- pression, and because the periaortic and pericaval lymph nodes are commonly involved by tumors of the genitourinary system, abdominal venography should be familiar to the urologist. Anatomy Figure 1 demonstrates ibe anatomic relations of the inferior vena cava. Figure 2 demonstrates llie major paracaval collateral circulation. Tlie communications of the inferior vena cava with the iliolumbar, vertebral, and azygos systems are abundant. It is because of this extensive collateral circulation that the clinical signs and syjnptoms of inferior vena cava obstiuction are often varied and capricious. Technique In 1956 we proposed three methods of obtaining vena cava- grams,^^' One method involves direct percutaneous translumbar puncture of the vena cava similar to that used on the left side for translumbar aortography. This method does not provide deimeatfon of the lower vena cava or of its anastomotic channels, and it is probably more hazardous than other methods since it is not possible to delect poslpuncture bleeding from the vena cava. TJie second method consists of bilateral femoral vein puncture with injection of 30 cubic centimeters of 50 per cent intravenous contrast material into each femoral ^ein simultaneously. The Other Advances in Urologic Radiofoscy 57 patient is prepared by catharsis as for intravenous urograpliy. Blood pressure cuffs are applied to llie tliigiis above the knees and a preliminary scout film is taken of the abdomen. Skin wheals are raised over the femoral veins approximately one fingerbreadth below the inguinal ligament and just medial to the pulsations of the femoral arteries. Deep infiltration about the vein helps to minimize the pain which may occur with extravasation of the contrast medium outside of the vein. The fenmral veins are punc- tured with 16*gauge, short, beveled needles attached to syringes, and when a free flow of hlood is ohtaiiied the needles aie connected to the limbs of an intravenous infusion set. Tliis technique pro- vides a method of determining when die needle is properly placed in the vein, and inainiuins the patency of the needle. A slow in- figure 3. Metiiod of alnlominal venography employing bilateral femoral vein puncture. Injections are made into tubing rather than directly into the \cin. Tliis minimizes risk of needle dislodgment from the vein during the injection. Note the Mood pren^ure cuffs on the thighs. 58 ADVANCES IN DIAGNOSTIC UROLOCr fusion of saline is allowed between injections of the contrast medium, and the dye can be injected into the tubing rather than into the needle, thus minimizing the cliance of dislodging the needle during the injection. Prior to tlie injection of the contrast material, the cuffs are inflated approximately to diastolic blood pressure, and the patient is asked to hold his breath and to strain slightly against the closed glottis. Rapid injection of the contrast material is not necessary, but it should I>e injected simultaneously on each side within a period of 10 to 15 seconds. Following completion of the injection, the needle is withdrawn from the tubing and the infu^iion is allowed to (low into the femoral veins. If a rapid cassette changer or Elema*Scb6nander changer is available, ex- Figure 4. Normal vena cavagrsm showing early reflux into the internal iliac s} stems and into the left ascending lumbar vein. Note the smooth con- tour and the straight course of the iliac veins and the \ena cava. Olher Advnnces in Urologic Radiology 59 posures are made heginning near llie end o£ injection at one-second intervals for six seconds. If a cliaiiger is not available, a roent- genogram at one-fifth second is made approximately five to eight seconds following the injection of contrast medium. This method is demonstrated in Figure 3. lliere is usually a flush reaction due to the rapid injection of contrast medium, and the usual pre- cautions should be taken as for intravenous urography. Figure 4 shows a vena cavagram obtained Iiy this method, demonstrating a noi mal vena cava with early reflux into the internal iliac and ascending lumbar veins. Figure 5 demonstrates a partial obstruction of the upper vena cava caused by a tumor thrombus extending directly from a bypeniepbroma of the right kidney. The more extensive filling of the iliac veins with cross communication in tlie presacral area is noted. Figure 6 demonstrates characteristic scalloping of the inferior vena cava by large lymph nodes involved Jjy metastasis from tesliciijar embryonal carcinoma. Extensive collateral circulation through the arcaded vertebral plexus is evidence of more advanced occlusion of the vena cava. Figure 7 demonstrates another use of abdominal venog- raphy. In this instance retrocaval ureter was demonstrated by tlie simulta77eous 777ferior cavography and calheter7zalio7) of the right ureter. A third method of abdominal venography involves percutaneous catheterization of one or both femoral veins by the Seldinger meiliod. This recent, sophisticated lechnirjue insures the best de- lineation of the vena cava 7ind its collateral channels, particularly when injection is performed with the automatic (Gidlund) injector and films are taken with the Eleina-Schonander unit. C/sfng tfifs technique, we have injected 25 milliliters of 75 per cent Hypaque into the catheters at a pressure of 2 kilograms per fecpiare centi- meter and have taken films at a rate of one per second for 8 seconds. This method also allows changing the position of the patient in order to obtain oblique and lateral views. F t^ure 5. Filling defect in the npper vena cava caused by a tumor ihrnm- bus extending from a hypernephroma of the right kidney. Partial obstruc' lion from this intraluminal thromhus has caused more extensive collateral circulation, evidenced !>> filling of the internal iliac systems. 62 ADVANCES IN DIAGNOSTIC UROLOGY Figure 7. Retrocaval ureter shown by ureteral catheterization and inferior vena cavagram. CYSTOURETJIROGKAPin’ 'Cunningham* first described urellirography in 1910. Initially he used 50 per cent Argyrol. Since tlial time a variety of substances have been employed, including suspensions of barium, bismuth, and thorium, solutions of potassium and sodium iodide, silver salts, iodized oil, and waler-soluble organic iodides, Between 1933 and 1955 urethrography was perfomietl primarily w’lh oily substances such as Lipiodol or lodoclilorol. However, because of the frequent reports of fatal oil embolism resulting from their u«e, ° these media were gradually replaced with safer contrast substances. In lecent years it has been common for urologists to Other Advances in Urologic Radiology 63 employ mixtures of water-soluble lubricating jelly and newer organic iodine compounds (sodium diatrizoale or sodium acelri- zoate).’^ In 1957 Thixokon was introduced as a result of earlier experimentation with combinations of organic iodides and lubri- cating jelly. Thixokon, a thickened aqueous solution of the so- dium salt of 3-acetamido-2,4,6-lri-iodo!>enzoic acid prepared with amioca, a nonjelling starch, is a product fulfilling the requirements of a safe, effective medium. The thixotropic property allows the medium to he injected into the urethra with comparative ease, and upon coming to rest, its viscosity lo increase so tliat it may be retained during the examination. Experience with this compound has shown it to he eminently salisfaclorj' either full strength or diluted.*® Urethrography is now employed in the form of retrograde injec- tion, voiding cystourellirography, and “choke” urethrography. Retrograde uretiirography, with the patient in the oblique position, lias been used largely with tlie Brodny clamp in the male. Voiding cystouretlirography has enabled urologists lo demonstrate voiding dynamics wliich were impossible lo visualize with the injection method alone. Figure 8 shows a comparison of a retrograde uretlirogram willi a voiding urethrogram in a patient with multiple urethral strictures. The voiding cystourethrogram has been helpful in demonstrating constrictions of the bladder neck due lo fihromuscular hyperplasia. It has been particularly useful in children in whom the diagnosis of concentric contracture of the bladder neck lias been equivocal with other diagnostic modalities. In this technique the bladder is fdled by catheterization or by intravenous urography. In callielcrization 15 per cent sodium acetrizoate or sodium diatrizoale has proved satisfactory. Films are taken both during micturition and after voiding, the latter Ireing made to record residual contrast medium or ureteral reflux (see Chap. 2). Tiie characteristic de- formity has been one of proximal urethral dilatation, which has been called the “acorn deformity” by Licit® and the “carrot sign” 61 ADVANCES IN DIAGNOSTIC UKOEOCY Figure 8. A comparison o( a relrogratle utelUrograiu ’Aith a voiding ute* thrograra in a patient witit multiple urethral strictures. I)y Hinman.'^ Tlie amounl of urelliral tieformily varies nilli the degree of bladder neck oljsliuclion. Figure 9 demonstrates a cliaracleristic cystoureibrograin in a cii'ild willi Idaclder neck contracture. “Choke” voiding urethrography, devised by Peatman,"* refers to the discharge of radiopaque medium from ibe urethra against resistance. This teclmique piovides belter filling of the anterior and posterior urethra for diagnostic purposes; the filling is accom- plished by mechanical narrowing of the uiethral meatus or by llie Use of a highly viscous medium. The bladder may be filled with a radiopaque medium by intravenous injection (excretory urog- raphy) or by iiistinalion of ibe medium ihrougli a urellual catheter. If the procedure is performed as part of the excretory uro- gram, it is advisable to ««e a double dose of medium and to provide the patient willj two gla-ses of water after the five-niiiiule film has been taken. When the patient expresses a desire to void, a rubber band is applied around the distal penis, the patient is Other AiJvances in Urologic Radiology 65 Figure 9. C)sloure:hrografn tlemonffratlng “acorn deformify” l)T>ical of bladder neck conlraclure. instructed to void, and an oblique film is taken during the \oiding. A lirodny clamp has also Iwen used to provide a “choke” through which the patient voids. Because a mechanical type of “choke” urethrography is diffi- cult to achieve in women, a thickened medium such as full- strength Thixokon has been employed to produce a “hydro- kinetic choke.” Figure 10 shows a normal retrograde urethrocystogram, a “choke” \oiding rysloure’hrogram in a male, and a short stricture of the hulhous urethra in another “choke” uretlirogram. Occasion- ally the “choke” technique will also aid in the demonstration of vesicoureteral reflux. figure 10. A ciioke voiding cystourethrogram in a male (center), demon«trai5ng improved filling o( live urethra ; compaieil to the retrograde injection method (left). A short stricture is well delineated in another “choke” voidii urethrogram shov*n at the right. Other Advances in Urologic Radiology 67 Urethrography is an integral part of urologic diagnosis. The voiding cystourethrogram and the “cJioke” urethrogram are both valuable recent additions to the technique, and the introduction of water-miscible contrast medium of ideal viscosity has added to the safety and utility of the procedure. LYMPHOGRAl’II Y IN UROLOGIC DIAGNOSIS Lymphography, the radiographic demonstration of lymphatics and lymph nodes, is a relatively recent addition to roentgenology in this country. In the past few years several reports of lymphog- raphy in urologic diagnosis have stres«ed its application in the field of urogenital malignancies and, mote specifically, in (he detec- tion of lymphogenous spread of tumors of the testis, prostate, bladder, penis, and kidney.^' This technique has also been advocated in the diagnosis of retroperitoneal tumors responsible for ureteral obstruction. Combination studies employing intrave- nous or retrograde pyelography, abdominal venography, and lymphangiography provide tite most accurate diagnosis of retro- peritoneal lymph node disease currently available. However, tiie method of lymphangiography is more time-consuming and difficult than that of abdominal phlebography and its applications are there- fore somewhat more limited. Terlinique A lymphatic on the dorsum of the foot is made visilde by absorp- tion of “direct sky blue” wliicli is injected subcutaneously into the first well space.^* One-half centimeter on eacli side is ade- quate. The l>Tnphalic is i«o1aled, and if a temporary ligature is placed about it proxinially, the vessel will become prominent enough to facilitate the threading of a 30-gauge needle into its lumen. The needle is fitted with a polyethylene tube attached either to a 20-cubic-centitncler sjTinge or to a mechanical injector. 6y ADVANCES IN DIAGNOSTIC UHOLOCY Approximately 12 ciihic cenlimelers of Ethioclol, an iodinated ethyl ester of poppy-seed oil, is injected at a slow rale varying from 0.2 to 1.0 cuhic centimeter per minute. The time necessary for a lynii>hangiogiapIiic study' is from 2 to 2V^ hours. Too rapid an introduction of the conliast material will result in extravasation into llie soft tissues, iherehy pioducing pain and poor lymphatic absorption of tlie dye. After the injection is complete, roentgeno- grams are tahen of the thighs, pelvis, and abdomen. Oblique and lateral films are extremely useful. If films aie taken immediately after injection, the lymphatics will he visible as illustrated in Figure 11 (lymphangiography). After approximately 24 hours the dye is seen only in the lymph nodes (lymiphadenography), and remains there for as long as two to three inoiiths. After injection of the lymphatic \eseel of llie leg, tlie first nodes visualized are llie super ficial inguinal e lands. Tlieieafter the direc- tion of lympliatic drainage is toward the deep inguinal nodes, and then towaid the deeper nodes along (he external and common iliac ve&sels. Subsequently the paiacaval and para-aortic notles are visualized, and eventually drainage is into the cisterna chyli. Tnenty-four and diWioiir roentgenograms aie best for visualizing the lymph nodes. Lymphatics of the penis may he used for injection, and in lid* case an incision is made on the dorsum of the penis and a total of 2 to 4 cubic centimeters of contrast medium is injected for subse- quent visualization of the inguinal and pelvic nodes. The normal lymph node is usually round or oval in shape, often has a scalloped edge, and uithin usually lias a homogeneous leticulated pattern. When the lymph node is involved by tumor, irregular C,Uh\g deCecte wrU Ivc veew uither centrally cv at tlie margin of the gland. If there is complete replacement of llie lymph node by tumor, there may be gaps in the spacing of lymph nodes along the chain. Lymphatic obstniclion is evidenced by dilated afferent vessels as well as by collateral and retrograde flow of llie contrast medium. Other Advances in Urolo^ic Radiology f>9 Figure 11. Lymphatics of the |«lvis, mamp nodes to retroperitoneal masses with and without urinary involvement. 72 ADVANCES IN DIAGNOSTIC UROLOGY Com/?licolionj The only significant complication of the tliagnostic technique of lymphangiography is pulmonary infarction ihie to oil embolism. This usually results from the madvectent injection of small veins rather than lymphatics. However, a pathway of lympliatic*venous communication^" is also a source of oi! embolism. Small amounts of contrast material and slow rales of injection nill usually oliviate oil embolism. Some palienis experience pain in tlie calf or the dorsum of the foot at the time of injection; this is also minimized by slow injection. In summaiy, lympliography is a technique which can be com- bined with other procedures familiar to the urologist. It is particularly valuable m cases in which retioperitoneal and pelvic lymph node dissection is being done. Although the procedure is arduous, and its application is limited, the urologist may find it helpful in selected diagno'^tic and therapeutic problems. n ETERENCES 1. Crabtree, E. C. Venous invasion due to urethrograms made with Lipiodol. /. Urol. 57:380, 1917. 2. Cunningham, J. H. Roentgen rays. Tr. Am. A. Genilo-Vrin. Sur- geons. Pp. 369-371, 1910. 3. Davis, L. A.. Lid), R., Howerton, L., and Joule, W. Lower urinary tract in infants and children. Radiology 77:14.5, 1961. 4. Dos Santos, R. Presentation de radiographie: Phlehographic d'une veine cave inferieure sutures. /. Urol., Paris 39:586, 1935. 5. Farinas, P. L. Abdominal \enographj. Am. J. Roentgenol. 58:599, 1947. 6. Femicola, A. K. Extra-ur^hral conflnes of urethrographic contract medium. J. Urol. 06:132, 1951. Other Advances in Urologic Radiology 73 7. Fisher, H. W., and Zimmerman, G. R. Roentgenographic visualiza- lion of lymjjh nodes. Am. I. Roenigenal. 81:517-531, 1959. 8. Hinman, F., Jr. Personal communication. 1961. 9. Holts, S., and Powers, W. E. Inferior vena cavagrams. Radiolog) 70:583, 1962. 10. Kaufman, J. J. Experiences withThixokon: An aqueous, thixotropic uretlirograpliic medium. J. Vrol. 78:188, 1957. 11. Kaufman, J. J., and Burke, D. E. Abdominal venography ; Technique of roentgen visualization of the inferior vena cava. Am. J. Roentgerjol. 76:807, 1956. 12. Kaufman, J. J., Burke, D. E., and Goodwin, W. E. Abdominal venog- raphy in urological diagnosis. J. Vrol. 75:160, 1956. 13. Kaufman, J. J., and Russell, M. Cystourethrography : Clinical expe- rience with the newer contrast media. Am. J. Roentgenol. 75!88-l. 1956. 14. Kinmonth, J. B., Taylor, G. W., and Harper, U. A, K. Lymphangi- ography; A technique for its clinical use in the lower limb. Brit. M. /. 1:910, 1955. 15. May, R. E., and Dogash, M. Lymphangiography as a diagnostic adjunct in urology. /. Urol. 87:208, 1962. 16. Mellins, H. Functions of (he vertebral verjous circulation. Ball. Vniv. Minnesota M. Found. 22:237, 1951. 17. O’Laughlin, B. ]. Roentgen visualization of the inferior vena cava. Am. J. Roentgenol. 58:617, 1917. 18. Olivier, C. Technique dc la radiographic de la veinc cave inferieure. Mem. Acad. dur. 77:324, 1951. 19. Pearman, B. O., and Miller, J. Choke voiding cystourethrography. Scientific exhibit, Section on Urology, llllh Annual Meeting, A.M.A., Chicago, June 2-I— 28, 1962. 20. Pereiras, R., and CaMellanos, A. Diagnostico radiologico de la tlirombojdebitis dc la cava inferior. Arch. Med. Inf. 15:98, 1916. 21. SchafTer, B., Gould, R. J.. Wallace, S., Jackson, L., Ivker, M., Leber- man, I*. R., and Fetter, T. R. Urologic applications of lymphangi- ography. J. Urol. 87:91, 1962. 74 ADVANCES IN DIAGNOSTIC UROLOGY 22. Shanbrom, E, and 2heutlin, N. Radiographic studies of the lym- phatic system. AM.A, Arek. Jnt. Med. 104:589, 1959. 23. Stable, £. P., Milanes, B., Casanova, R., and Bustamante, R. Arch. Med., San Lorenzo 1:452, 1950. 21. Viamonte, M., Jr., Myers, M. B., Soto, M., Kenyon, N. M., and Parks, R. E. Lymphography: Its role in detection and therapeutic evalua- tion of carcinoma and neoplastic conditions of the genitourinary tract. /. Urol. 87:85, 1962. 25. Wallace, S., Jackson, L., Sdiaffer, B., Gould, J., Greening, R., Weiss. A., and Kramer, S, Lymphangiograms: Their diagnostic and thera- peutic potential. Radiology 76:179, 1961. RENOVASCULAK HYPERTENSION: 5 . CLINICAL CHAU ACTERISTICS AND DIAGNOSTIC TESTS MORTON H . MAXWELL AND JOSEPH J. KAUFMAN The association ])etvveen renal disease and hypertension has been recog!ii7ed since the time of Richard Bright.’- The classic experi- ments of Goldblatt-'* in 1934 demonstrated tliat interference with the renal circulation in dogs by clamping the renal artery’ could produce sustained arterial hypertension identical liemodynamically to essential liypertension in man. Kohlsteadl and Page^^ showed that a change in pulse pressure in the renal artery, not necessarily a diminution in blood flow, may be responsible for the elevation of blood pressure. Current work suggests that the juxtaglomerular cells of the kidney act as stretch receptors, changing their rate of secretion with ciianges in tJie stretch in tlie walls of the afferent arterioles.^’’ A decreased perfusion pressure to a kidney causes a release of renin’*’ and hypergranulalion of the juxtaglo- merular cells,®’ suggesting that, as originally proposed by Goor- maghtigh,-' renin is released from tlie juxtaglomerular apparatus granules. TJie theory that a humoral pressor mechanism plays an important if not exclusive role in the initiation and early stage of renovascular hypertension, and possibly in the chronic pliase as well, is held by most investigators.®"’®’ 76 ADVANCES IN DIAGNOSTIC UROLOGY Extracts of kidney tissue contain a proteolytic enzyme, renin, uJiich acts on a protein substrate produced by the liver with the formation of a io-assay techniques. Clarification of the role of these pressor sul)stancc« must therefore await more specific methodology . The first clinical counterpart of the Goldhlalt experiments v^ns the report in 1937 by Butler'® of the disappearance of liyperten* sion following the removal of a pyclonephrilic kidney in an 8-year- old l)oy. With the first wave of entliusiasm in the ensuing decade, many clinical reports appeared purporting to cure hypertension hy nephrectomy. However, in review articles in 1948 and 1956 Homer Smith*'' noted that of 575 nephrectomies performed in liy^jer- tensive patients with demonstrated or suspected unilateral impair- ment of renal function, the cure rale was 26 per cent (149 patients). Because of tltese observation-, and tlie possibility tliat many negative results were not reported, extreme caution was urgeil in the use of nephrectomy for cure of hypertension. Only 14 of the 149 cured patients had lesions of the renal arterial .system; the patliogenesis in Iwo-lbiitls of the patients was a'-crihed to pyelonephritis, atrophic kidney, or hydronephrosis. TJiis may lie contrasted with the predominance of renal arterial lesions in suli- sequent reports. The development of the teclmiquc of Iranslumhar aortog- rapliy”" *■ offered an accurate means of visualizing the main renal arteries. Howard and associates'"'®^^* emplia-izcd llie value of individual kidney function studies in the feelection of hyperten- sive patients for nephrectomy. They also demonstrated the need for assessment of all available diagnostic tools, including suggestive Renovascular Hypertension 77 history, radiologic evidence of disparity in kidney size, and renal angiography. The radioisotope renogram, developed hy Taplin, Meredith, Kade, and Winter,®* made avaijaldc a simple and innocuous means of detecting dis{)arily in kidney function and was rapidly employed in the appraisal of patients ivith hyperten* sion.*' The emergence of these diagnostic procedures was par* ticiilarly advantageous during a period of rapid advance in (he entire field of vascular surgery. Thus tlie preferential operative procedure for renovascular hypertension is now considered to he an arterial reconstructive procedure rather than nephrectomy.'’*® IKCIUENCE AND CLINICAL C II A It A C T E U 1 ST I C S incidence Illackman^ examined the renal arteries at autopsy in 2 com* parable series and noted significant arteriosclerotic plaques in one or hoth renal arteries in 86 per cent of 50 hjperlensive cases as compared vvitli 10 per cent of 50 normolensive cases. Measure- ment of the lumen of (he renal artery was undertaken after fixing and staining the points of greatest narrowing. Lisa, Eckstein, and Solomon'*’’* used graduated arterial sounds to measure renal arteries and compared these inca=urcnienls with Blackman’s find- ings. They could discover no relation hetween the size of normal nonsclerotic vessels as measured hy sounds in the unfi.xed state and the size found in the fixed stained specimens. The average diameter of the renal artery in the hypertensive subjects did not significantly differ from that of the normotensive controls. Extreme stenosis of the renal arteries did not occur in the nonnolensive group hut was found in 2 of 56 (4 per cent) hypertensive subjects. These figures agree with clinical e.\perience more closely than do those of Black- man, whicli may well he factitious hecau=e of the fixing technique. In doing arteriograms in “carefully selected cases,” Poutasse, Duslan, and Page"" found occlusive renal arterial disease in 131 of 7ii ADVANCES IN DIAGNOSTIC UROLOGY 427 patients (31 per cent), PerlolT and associates®® in 54 of 110 (SO per cent), and Hunt and associates®® in 90 per cent. Of 260 consecutive patients with severe hypertension who undenvent aortography, Sutton, Brunton, and Starer*^ found 26 (10 per cent) with renal artery stenosis. Accurate estimates of the true incidence must await studies of large groups of unselected hypertensive individuals, with all available diagnostic procedures utilized. Smith’s estimate®* lliat less than 2 per cent of the hypertensive population are candidates for therapeutic renal surgery is an underestimation in view of the newer, presently used techniques, and our experience would indicate that between 5 and 10 per cent of the hypertensive population arc candidates for surgical treatment. Clinical Characterislica Perera and Haellg®^'”® and Howard and associates®® suggested that hypertension associated with unilateral lenal disease is gen- erally severe in intensity, of abrupt onset and short duration, rapidly progressive and accompanied by most of the signs and symptoms of accelerated (malignant) hypertension. Subsequently other investigators®' i^*®*-*®* suggested that the appropriate tests for renovascular hypertension generally should be limited to patients with certain clinical criteria, which can he summarized as follows: (1) the onset of Iiyperlension in young (under 30) or elderly (over 50) individuals, especially those w’ilh a negative family histoiy- of hypertension; (2) a recent unexplained worsen- ing in the severity or symptoms of previously benign hypertension; (3) the presence of malignant hypertension; (4) a history suggest- ing tlie possibility of a renovascular accident, such as unexplained abdominal or flank pain, renal trauma, or peripheral emboliza- tion. As more hypertensive subjects are screened by appropriate tests, however, it is apparent that renal arterial insufliciencj’’ may mimic all tjqies of essential hypertension and even primary aldosteronism.*®' Among our group of 44 pa- /?enofaicuf(ir Hypertension 79 tients who have been followed for at least one year following operation, 10 had hypertension for longer than 5 years, and 3 pa- tients with longstanding liyperlension of 14, 15, and 17 years were completely cured Ijy operation. Twenty of tliese 44 patients had mild to moderate hypertension as Judged by retinal changes, diastolic blood pressure, and evidence of left ventricular hyper- trophy, and only 19 had an unusual age of onset (under 25 or over 50 ) ; neither the severity of the hypertension, the age of onset, nor the family history hore any relation to the outcome of opera- tion. Tlie Cleveland Clinic group,"^ in a comparison of 139 patients witli renovascular liypertension and 127 patients with essential hypertension who were investigated hy means of renal angiography, reports no striking difference between tliese 2 groups ivith regard to age of onset, duration of hypertension, retinal changes, or family history. Furthermore, none of these parameters has predictive value as to surgical cure or failure. Hypertension secondary to renal arterial lesions can be piesent in some patients for many years without entering the malignant pliasc and without causing irreversible changes in the opposite kidney. The affected kidney may well lie “protected” from the effects of hypertension and thus be the belter of the two kidneys. This does not imply that hypertension secondary to unilateral renal ischemia may not become self-perpetuating. Although there w'as considerable overlap, we observed a positive correlation between the duration of the liypertension and the cure rate follouing operation.®' Since the tests necessary' to rule out renovascular hy- pertension completely (especially renal arteriography and indi- vidual kidney function studies) are loo expensive, complex, and hazardous to warrant their routine u«e, they' should he resei^'ed ftir those patients with “inappropriate liyTicrlension,” as described above. IlecauBC the prognosis of patients with severe or accelerated hypertension is extremely poor, even with adequate drug therapy, \se think that all diagnostic procedures ore al«o indicated in this group. 80 ADVANCES IN DIAGNOSTIC UROLOCV Since a significant portion of reported surgical cures, has taken place in patients with atheromatous plaques of the renal arteries, individuals with evidence of atlierosclerosis in large and medium- size vessels and concomitant hypertension must he especially sus- pect. Several authors have noted the presence of systolic abdominal bruits associated with renal artery stenosis.”' The murmur is often liut not invariably best heaid in tlie mtdiine in the epigas- trium with transmission to the affected (or more severely affected ) side. In our experience it is often necessary to press deeply beneath the costal margins in order to hear the nuinnur. The bruit may at times be audible over tlie costovertebral angle'"* or over the femoral artery.” The bruit may l»c high-pllchec distinguished from a systolic murmur transmitted from the heart. !• A T n O I. O C V To ascertain if the hypertension is caused by and not just coin- cident with narrowing of the renal artery may be as difficult for the pathologist as it is for the clinician. Ynile,*”” in reviewing all reported nephrectomies prior to 194i, accepted only those cases in wJiicli no possible mechanism for hypertension could be present other than the main renal arterial lesion. Only three cases fulfilled this criterion; in these three cases the affected kidney did not demonstiale arteriolar sclerosis, hut parenchymal fdirosis and lymphocytic infiltration were present. I«cliemic tubular atrophy was first reported by Berlhrong.*” The niicro'-copic findings are primarily in the proximal convoluted tubules and are very dilTerenl from those of uncomplicated pyelonephritis.'®’ The glcmeruli, wliich arc less sensitive to ischemia, show' little or no histologic alinonnalily when tubular Renovascular Hypertension JJ3 damage issliglil. In more severely affccled cases, ihickening of the capillary basement membrane, fibrosis of Boivman’s capsule, and widespread glomerular sclerosis occur. Lymphocytic infiltration and fibrosis of the tubules occur in severe tubular ischemia. Prominent intrarenal vascular changes on the opposite side, in contrast to normal arterioles in the ischemic kidney, were reported by Laforet,'*® Bauer and Forlies,* and Brown and associates.*® The presence of this type of tubular atrophy in pyelonephritis compli- cated by liyperlension has also been described by Kincaid-Smith.^* Bertbrong®® was able retrospectively to predict correctly the alle- viation of hypertension by nephrectomy in 14 of 15 cases ba.sed on iscliemic tubular changes; llie fifteenth ca«e bad no morpliologic lesion except hyperplasia of the juxtaglomerular apparatus. Turgeon and Sommers,®* using the juxtaglomerular cell count, found significant hyperplasia and some increased granularity of juxtaglomerular cells in the affected kidney in 20 proved cases of renovascular Iiypcrtension in men. In 5 contralateral kidneys, cell counts were reduced significantly in comparison with the affected kidneys in the same patients. The number of juxtaglomerular cells decreased with increased duration of the hyi>cjlension. This ohser- valioii is in agreement with the theory that hypertension i.s initialed through a renin-angioteuvin mechanism, whereas hypertension of long duration is sustained by another mechdni«m.®* **® The most common lesion in the renal arteries is the atheroscle- rotic plaque.®® The lesion may he an eccentric plaque or a con- centric zone of atheroma formation with superimposed thrombosis. The lesion may involve the main renal arterj’ or a branch artery and is frequently seen at the mouth of the renal artery. The atherosclerotic lesion is more likely to occur in males in tlie older age group having atheromas in other arteries. First described by Leadbettcr,'*® fibrous h>7»crplasia of the renal arteries, either of the muscularis, intima, or adventitia, has been noted with increasing frequency since the advent of aortography, which pennils a characteristic beading of the arteries to he 82 ADVANCES IN DIAGNOSTIC UROLDCY This type of lesion is found predominantly in females in the younger age group. Its pathogenesis is obscure, with arteritis, a congenital abnormality, or trauma produced by ptotic kidneys’® being implicated (see Chap, 1). Hypertrophy of the media produces irregular and extreme narrowing of the renal arterial lumen, with focal areas of thinning and aneury-smal dilata- tion, Bilateral involvement of the renal arteries is frequent and ex- tension into the segmental branches occurs. Congenital steno->is, aneurysm, arterial emholi, arteriovenous fistula, Takayasu’s di- ease, and arterial tumors are rarer causes of renovascular disease. DIAGNOSTIC TESTS There is as yet no single test tliat is diagnostic of renovascular hypertension. If, as has been inferred from experimental studies, the elevated blood pressuie is caused by the secretion of a humoral pressor substance from the involved kidney, llien the simple measurement of this substance by percutaneous catheterization of the renal veins should preclude the need for further tests. Altliough preliminary studies in a few patients are encouraging,®® the lack of agreement on methodology for the measurement of physiologic quantities of renin or angiotensin makes the measure- ment unfeasible at llie present time. The majority of renal arterial lesions are unilateral. Further- more, even nitli bilateral involvement it is unlikely that both kidneys will lie alTecled to an equal degree. Threfore any procedure which is safe and which serves to detect disparity in kidney size or function is oF value as a screening test. Both the radioactive renogram®®' *®® and the intravenous pyelogram sen’e tliis purpose. Tliese tests are not entirely specific for renovascular hypertension nor predictive of surgical cure, and by definition they well yield false positive results; for example, disparity between tlie two kid- neys may occur in a variety of urologic conditions with or without Renovascular Hypertension 83 hypertension. The crucial question is ^vhethe^ either test or a com- hmation of botli tests is sensitive enough to discover the majority of renal arterial lesions. If the renal hemodynamic changes secondary to partial arterial occlusion result in specific functional patterns, individual kidney function tests sliould be diagnostic. In 1956 Howard and asso* ciates^'* reported that measurement of urine volume and sodium concentration from each kidney yielded a pattern which was diagnostic and predictive. Modified tests were subsequently de- scribed by Birchall and associates,® Rapoport,^^ and Stamey and associates.*^'®® The application of these tests to patients with various types of liypertension lias yielded discordant results. The single technique which thus far has been of greatest value in the diagnosis of renovascular hypertension is the renal arterio- gram.®' It must be remembered, however, that false positive and negative arteriograms occur and that the demonstra- tion of an occlusive lesion of the renal artery does not by itself prove that it is responsilde for the hiTierlension. Distinction must be drawn in the ensuing discussion between the terms diagnostic and predictive. In most clinical disorders which are curable by operation, the terms would be s>monymous. In renovascular hypertension, however, this is not the case. In llie animal with experimental renal hypertension, the evidence strongly suggests that, althougli the early mechanism is humoral, at a later stage extrarenal factors come into action which may in themselves he sufficient to sustain the elevated Idood pressure.®'*'''*’®^ An alternative explanation for the perpetuation of the hypertension may lie the development of arteriolar lesions in tlie opposite kidney, presumably caused by the hyperten>5ion itself, as demonstrated in rats by Wilson and Byrom.®’ It is not known whether these events occur in the human being, and the exact time relationships are uncertain. It can he seen, however, that present techniques may at times be diagnostic without lietng predictive of surgical cure, if these secondary mechanisms have already come into play. This may nt ADVANCES IN DIAGNOSTIC UROLOGY explain some of the reported difficulty in predicting the outcome of operation vxith available metliods.*’’ RatUoisolope Reno^ram The chief advantages of the radioisotope reiiogram are its simplicity and safety, wbicli permit it to be repeated numerous times when necessary. The proceduie consists merely of obtaining a radioactivity curve externally over each kidney area after intra- venous injection of certain radioactive substances (see Chap. 9). Normally the renograni curves arc identical from both kidney s Although pieliminary e^^ort^ are being made to quantitate the procedure,'*® interpretation is at present purely qualitative and consists of visual compaiison of the two curves (Fig. 1). Block, Hine, and Burrows'” utilized an electronically integrated ratio between the renal counting rales. Artifacts may be caused by im- proper placement of the scintillation counters. The height and shape of the curse are affected by such factors as type of collima- Figure 1. Rathoisolo[>e renogram of a 36-)ear-oId woman wilh hyper- tension secondarj to right renal arterial stenosis. Note diminidied vascular spike (pha-e 1), flattening of secretory phase (phase 2), and slow declina- tion (phase 3) commensurate with smaller urine volume and slower flow rate on the ischemic right side. Renovascular Hypertension 85 tion, rate meter speed, position of patient, hydration, and Uiickness of the body Avail. Despite differences in precise techniques, sev- eral reports have indicated that the radioisotope renogram is a more sensitive index of renal dysfunction in a variety of urologic and parenchymatous disorders Uian is the intrave- nous pyelogram,'"’ although some investigators'*"' disagree. Of do patients who underwent surgery for the cure of reno- vascular liyperlension, 35 had discrepancie^ in renal function discernible with the radioisotope renogram,'’* and the renograms for 5 patients were read as symmetrical. Of these 5 patients, 3 had lesions of the main renal artery. Two of the 5 patients had unilateral renal abnormalities on the intravenous pyelogram. Thirty-seven of llie 40 patients had intravenous pyelograms. Eiglit failed to show unilateral ahnormalilies; 5 of these 8, however, had abnormal renograms. Hie positive renograms and pyelograms did not always coincide in the same patients, liut the comliination of tlicse tests served to identify 37 of the 40. In agreement wiili tfiese data. Block, Hines, and Burrows*® reported that, of 15 patients with unilateral renal hypertension, all lind abnormal renograms while only 12 liad abnormal intra- venous pyelograms. In a few inslances, unilaterally abnormal renograms have been noted in jialients willi apparent essential hypertension.*"' It is conjectural whether these results are artifaclitious due to variations in technique or whether they indicate that at times .signilicafit inequality of function exists in essential hypertension.* The simplicity and sensitivity of the radioisotope renogram appear to make it a useful screening procedure for the detection of disparities in renal function in hypertensive patients. The reno- gram is not a specific diagnostic test, and Avlien it is abnormal, further studies arc indicated to delineate the exact nature and anatomic location of the lesion. Standardization of equipment, the widespread u«e of radiniodinated Hippuran, and newer renal iio ADVANCES IN DIAGNOSTIC UROLOGY scanning lecJitiiques"® may increase the specificity and sensitivity of radioisotope studies of llie kidneys. Tlie techniques of renog- raphy are discussed in Giapter 9. fnlrni'c/ioiis Pyelogrnm The main pyelographic findings which Iiave been described in renal artery stenosis are: 1. Decreased size of the affected kidney (Fig. 2). Connor and associates'^ in 1954 noted atrophy of the ischemic kidney in some cases. Dustan, Page, and Poiitasse*" confirmetl this impres- sion, and in a review of 128 patients with arleriographic evidence of renal arterial occlusive disease they found that disparity of length between tlie two kidneys of 1 centimeter or greater was present in 70 patients, as compared to only 8 of 127 subjects with essential hypertension. Unequal kidney sire was the onl) nrographic abnormality in 45 of the 70 patients. Brown and associates'^ reported that in 10 of 19 patients wiili renal artery stenosis in ^hom pyelography was perfoimeil, tlie aiTected kidney was smaller than its fellow, but in only 5 of tlicsc patients was the difference in length greater than 1.5 centimeters. In no patient was the unaffected kidney the smaller one. Scott and associates'^^ stated ihni of 80 surgical patients 56 per cent had a disparity in renal size of greater than 1.5 centimeters, but that .^0 per cent bad kidneys of equal length. In comparing kidney sizes, it should be recognized dial in nonnal individuals the left kidney is somewhat larger Uian the righl"^' and lliat this difference in one series'’'^ averaged 0.8 centimeter. Altliough no figures were proentwl, Ilodson’" stated that in an analysis of over 700 pyelogiams “one of the most striking findings is the symmetry’ displayed by normal kidneys.” A difference between the long axes of the kidneys of over 1.5 centimeters, particularly with a nonnal jielvioealyceal pattern, is considered to be strongly suggestive of renal artery stenosis.’^" In 24 of 27 cases of proved renal artery stenosis, the kidney on Renovascular Hypertension 87 Figure 2. Intriivenous urogram showing disparity of kidney size in a paVient w\io«e aortogram shows s\eno«is ol ihe right rena^ artery (fihro- mu«cular hyperplasia) and whose renogram is seen in Figure 1. tlic affected side was smaller, Uie difference exceeding 1.5 centi- meters in 15 instances.*^ The interesting observation lias been made that shrinkage of the normal kidney (as measured radiologically) of up to 40 per cent may occur during anesthesia or periods of ADVANCES IN DIAGNOSTIC UROLOGY hj'potension.’*’' Furlhennore, ca^es of unilaterai ischemic renal disease showed asyminelrical degrees of shrinkage hetween the 2 kidneys, the unafTected kidney shrinking the mosl.^" Comparison of kidney length during the “nephrogram” phase of aortograpliy, when relative hypotension due to medication or to the procedvjre has occurred, is therefore subject to error. Renal artery stenosis may he represented in pyelography para- doxically hy higlier contrast and Ijeller visualization on the affected side tlian on the normal side, unless severe renal structural damage has occurred."*^ Better concentration on Uie side of tlie stenosis was in fact seen in 7 of 19 patients with renal artery stenosis.^"’ Dustan, Page, and Poutasse,”* conversely, emphasized a de- creased concentration on the affected side in the 5-minute film, a*» have Palubin«kas and Wylie.®* Scott and associates’* report that in 80 patients 20 per cent had a decrease and 30 per cent an increase in concentration on the involved side. In their more recent retrospective analysis, Dustan and a'^sociales®'* found that 47 of 128 patients Itad unequal concentration: decreased con- centration in 36, increased concentration in 6, with unilateral non- functioning kidneys in 5. Sutton ami associates*’ and Kaufman and associates'*® noted that in leiial artery stenosis pyelographic differences (increased calyceal density in the affected kidney) are made more prominent when the inlrawnous pyelogram Is per- formed during a water diuresis following an oral >s'ater load. It is thought that the ischemic kidney continues to excrete a con- cenliated urine under condition^ of a water load, uliile the oilier kidney produces a very dilute urine (Fig, 3). Comparison of relative concenlralion is, of nece>sily, inexact and subjective. Variations in techniques of pyelography (use of vasopre«-sin, dehydration, hydration), the number of films and times of exposuie following injection of the opaque medium, over- lying gas sliadons, and other artifacts make it difficult to compare different series. 90 ADVANCES IS DIAGNOSTIC UROLOGY 2. Difference in “appearance lime." Allliougii delayed ap- pearance in tlie calyceal syslem lias been noted in some patients with renovascular hypertension,'^"’’* presumably these observa- tions refer to the 5-minute film, since in most hospitals this is die first exposure made. Because heretofore the intravenous pyelogram has been utilized largely to study anatomy rather than function, techniques vary %videly. It is not uncommon, for example, to inject the contrast medium over a 3-minute period and to apply ab- dominal compression in order to prevent rapid excretion and to obtain better calyceal delineation. Functional interpcetalion of urograms is usually limited to such statements as “impaired” or “poor function” and indicates inadequate calyceal filling in the late (10- to 30-minule) films. The recently developed technique of the rapid intravenous in- jection of contrast media within 30 to 40 seconds, with films taken at 1-mtnute intervals for the first 5 minutes, lias further enhanced the intravenous pyelogram as a lest of Individual kidney fnne* tion.***’ Using this technique, we have noted at least a 1-minute delay in. opacification of (he calyceal system in 20 of 21 cases of renovascular hypertension'*" (Fig. 4). A delay was noted in 500 control patients unless raiher pronounced unilateral obstructive uropadiy was present, and major untoward reactions from the rapid injection were not encountered. Sutton and associates*^ stale that unilateral “spasticity,” or undeifilling of the calyc^, is .«;uggeslive of renal artery stenosis, and was noted in 8 of 27 cases. A bilateral spastic appearance of the calyces is considereil of little significance, since it is not uncommon and often is caused by dehydration. Tliese author- caution, honever, that this abnormality may be due to other ca for example, iiinannnatory lesions or calculus. In a significant number of cases, “nonfunctioning” kidneys have been noted during intravenous pyelography. In these in- stances, when a retrograde urogram reveals an essentially normal pelviocalyceal system, renal ischemia should he strongly su«pectc (GFR)/" All of the te^ts iiiTOlve ureteral collection of urine from each kidney. The first clinical application of these physiolo^. was suggested hy Howard and associates,^* who noted ttiu series of 45 patients with presumed essential hypertension, m eluding 3 with severe hypertension of recent on«et, the portions of urine obtained simultaneously from both kidneys were nearly identical in volume and varied less than 5 per cent in sodium concentration. In 4 other patients with severe hypertension who benefited from neplirectomy, a reduction in urine volume (V) of 60 per cent or greater and a redurtion in sodium concentra- tion (Un») of 16 per cent or greater from ibe affected kidney were noted. In a more definitive report by 3 members of the same group, urine volume and sodium concentration in 58 patients witlj presumed essential byperlension were nearly identical from each kidney. Nine patients demonstrated at least a 50 per cent reduction in urine volume and a 15 per cent or more reduction in blood pressure following surgical procedures. In 8 patients willj radiographic evidence of unilateral renal disease in whom catlielerization study disclosed a decreased urine volume from the diseased kidney but equal or greater sodium concentration, ne- phrectomy did not result in a significant amelioration of blood pressure. Tlie authors did report, however, 2 cases with segmental renal arterial lesions in whom catheterization study revealed a 50 per cent reduction in urine flow but equal sodium concentra- tion, with relief of the hypertension following removal of the Arrdffcy hariag the Jerwer urine auiput. Fifteen to 20 pec cent of the catheterization studies were noninlerpretahle because of tech- nical dlflicullies.’^ Among rCtasons given for discarding test results were cessation of urine flow during a collection period, excessive leakage of urine around the ureteral catheters, inadequate urine volume, inconsistent results over several collection periods, and excessive amounts of blood in small volumes of urine. Reduction in urine \oIume of at least 50 per cent and reduction in sodium pi ADVANCES IN DIAGNOSTIC UROLOOV concentration of at least 15 per cent on the suspected side (positive Howard test) were utilwed subsequently by others as predicthe criteria in considering patients for surgery/'^' A number of investigators have used ibe Howard test in study- ing patients with main renal artery stenosis and have found ihb lest to be of Cures following nephrectom>, however, have been reported in patients with lesions of the main renal artery in which the volume wms reduced on the alTecled side while the sodium concentration remained equal to or greater than that of the normal side/* Xli'is is not unexpected since, as pointed out hy Birchall and associates* and hy Baldwin,* tlie actual U.Na may varj’, depending on the relative proportions of water and of sodium reabsorbed. False positive Howard tests have been re- ported/' Some of the patients on whom thc&e te«ts were performed had chronic pyelonephritis or iieplirosclerosis. Although it has been generally assumed by subseijiient workers that the Howard test is specific for renal arter>’ stenosis, it should he noted that, among the original four posile kidney, and the urine iiuilln concentration was at least 16 per cent greatei.*’” Although the Howard test was positive in 9 of 10 subjects with stenosis of the main renal artery, it »s empliasircd that this same test isns negative in 4 instances of segmental stenosis. Indeed, it is staled that segmental arterial lesions were discovered hy tliis procedure in 3 subjects having normal aorlograms. If tlic'sc results are con- firmed, the urea-ADH infusion technique may he more sensitive and specific than earlier technique*. Although the measurement of inuliii or PAH is sj»eciffcd by these investigators,'*'' creatinine determinations should lie of equal value and would be more readily available in the average lio-pital. Individual kidney function snidien of a 57-ycar-old male with occlusive disease of the right renal artery arc sliown in Table 2. Tlie tests confimi right renal i*clicmia according to ibc criteria of Howard, Hapopoit, and Slamey. In the technique of indiv'idiial kidney function tests, there are certain modifications wliicb are aimed at avoiding ureteral feakago, uuinterpretable results, and oilier prev iously described difTicuUies. All antih>'perterisive and saliurelic agents should he discontiiiuetl for a period of at least one week, uiiIcns the patient’-, condition is so precarious that this is medically contraindicated. Analgesia Renovascular llyperlension 99 Table 2. Split Function Sturly; Infusion of Urea and ADH Predicted GFIi-124 Predicted RPF-654 R L Urine flow {cc./min.) 0.5 6,2 CcR (cc./min.) 22 53 CpAU (cc./min.) 128 260 Na concentration (mEq./L.) 5.1 73 PAH concenlralion (mg. %) 572 91 Creatinine concentration (mg. %) 54 10.6 is accomplished with meperidine, 75 to 100 milligrams, and secobarbital, 200 to 300 tnilligrams. Saddle block may' be utilized. Starncy*^ attempts the insertion of a No. 8 polyethylene catheter iti eacli ureter. If this does not fit. No. 7, No. 6, and No. 5 are llton tiled successively, allowing the largest polyelltylene catheter which fits snugly to remain in place during the procedure. He states that appro.ximately 1 in 3 adult ureters will allow the No, 8 polyethylene catljeler, thereby reducing the incidence of leakage. In about 5 per cent of tests significant ureteral edema occurs, wliich may cause obstruction to urinary flow. Tliis may be relieved by the insertion of a smaller catheter past the ureteral obstruction. To minimize the edema, Schlegel and associates'^'^ have suggested the infusion of a 4 per cent urea solution following the procedure. We have encountered excessive morbidity from the use of polyethylene catheters and are currently evaluating teflon catheters for ureteral collections. To meet the Howard and Rapoport criteria, oral liydration may be used. When it is used, a urinary flo%v rate of at least 2 milliliters per minute in the unaffected kidney is advisalde, and hydration should begin orally on the night Iwfore the test. Fluids should be continued in the monnng and while the catheterization is being performed. If oral hydration does not produce adequate urine flows, fluids containing urea as an osmotic diuretic may be injected 100 ADVANCES IN DIAGNOSTIC UKOLOCY iiUra\enously. In our experience,*" ahliough increasing urinar)* sodium excretion, urea l\as not affected the relative amounts of sodium excreted hy cacli kidney. Serious doubts about the applicaldlity of individual kidney function te*-ts in Uie diagnosis of renovascular hypertension ha\e been raised by Balduin and as«ociatesi,^* ubo report functional disparity exceeding that found in nonnotensive subjects in dO of 50 patients udlb presumed essential hypertension." These authors postulate that the 2 kidneys are often affected unequally by lijjiei- lension. Tliese results are at variance with other studies in whicli patients with essential iiypeitension generally exhibited no signifi' cant functional differences lielween tbe 2 kidneys (GFR, KPF, UiMii, UiN, EFn., V) ® ’•'* the results also run counter to tbe widely held belief that in all stages of e«sential hypertension both kidneys arc affected equally. In the studies cited, tlie diagnosis of essential hypertension lias been made on clinical grounds alone. Until similar studies are performed on jutients in whom arteriog* raphy has been performed, final conclusions are not justified. S i; .tl M A R Y Renovascular liypertension is the mo>t common form of sec- ondary h) perlensioii and should be sought in all cases of “^atypical” Iiyperteii-sion and/or severe liypertension, especially ulien Jii>tory, physical examination, radioactive renogram, or intravenous pyelo- grain point toward a renal ischemic niecJianism for the hyper- tension. There is no single procedure uhich is diagnostic of a lesion and predictive of surgical cure; all factor^ in the history, physical examination, and laboratory studies, including individual kidney function and angiography, inu»t he considered before an operative jiroccduie is undertaken. Indeed, even ubeii a diagnosis is estaldislied, the efficacy of medical treatment or simple neplirec- tomy imi«t be weighed against the ojieralive mortality rale of Renovascular f/yperlension 101 djflicult arterial reconstruclrve surgerj' in patients with multiple arterial lesions. Operative results in appropriately selected patients are excellent. Renal artery stenosis as the cause of renal ischemia should be sought with careful scrutiny among the hypertensive population. ncrEHENCES 1. Baldwin, D. S. Function ol the separate kidneys in h)pcrtension of unilateral renal origin. Prog. Cardiovas. Dis. 4:134, 1961. 2. Baldwin, D. S., Hulet, W. M., Biggs, A. W., Combos, E. A., and Chasis, H. Renal function in the separate kidneys of man: 11. JJemodynamics and excreitoit of solute and water in essential hyper* tension. /. Clin. Invest. 39:395, 1900. 3. Bauer, H., and Forbes, C, L. Unilateral renal artery obstruction associated with malignant nephrosclerosis confined to the opposite kidney. 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The production ol persist- ent elevation of systolic blood pressure by means of renal ischemia. Expcr. Mai. 59:317, 1931. 27. Goorinaghligh, N. Existence of an endocrine gland in the media of the renal arterioles. Froc. Soc. C.\per, Biol. & Med. 42:688, 1939. 28. Harkness, S., Crockett, W. A., and Parrish, D. Experiments xrith and iiUeqiretation of the Dioilrast renogram. Clin. Res. C:107, 1958. 29. Hayne, T. P., Nofal, H. M., Carr, E. A., and Belerwaites, W. H. The u«c of I*-”-laheled contrast metlia in scintillation scanninjt of the kidney. /. Lab. & Clin. Med. 58:598, 1961. .30. Ilelmer, 0. M. Pressor substances in renal xein blood of hyperten- sives. M. Clin, B'orih America >15:309, 1961. 31. Helmer, 0. II., and Judwn, M'. E. The presence of vasocon«triclor and vasopressor activity in renal vein plasma of patients xvilh arte- rial hypertension. Proc, Council for High Blood Pressure Research: Renat, Eleclrolyle and Aulonotnic Factors, Am. Heart Assoc. 8:38, 1960. 10( ADVANCES IN DIAGNOSTIC UROLOGY 32. Hoclson, C. J. Ph) siological changes in size of the human hidne}. Clm. Radiol. 12:91, 1961. 33. Howard, J. E., Berllirong, M., Gould, D. M., and Yendt, E. U. Hy- pertension resulting from unilateral renal vascular disease and its relief hy nephrecloinj. Bull. Johns Hopkins Hasp. 91:51, 1951. 34. Howard, J. E., Connor, T. B., and Thomas, W. C. A functional test for detection of hypertension produced h> one kidney: Preliminary studies. Tr. A. Am. Physicians 49:291, 1956. 35. Hulel, W. H., Baldwin, D. S., Biggs, A. W., Combos, E. A., and Cliasis, N. Renal function in the separate kidneys of man: I. Hemodynamics and excretion of solute and water in normal subjects /. C/m. /nvest. 39:389, 1960. 36. Hunt, J. C., Fairbairn, J. F., Tauxe, N. W., Kincaid, 0. W., Davis, G. D., and Mayer, F. T. Symposium on hypertension associated with renal artery disease. /Voc. Sta/f A/eei. Mayo Clin. 36:679, 1961. 37. Jaenike, J. R. Urea enhancement of water reabsorption in the renal medulla. Am. 1. Physiol. 199:1205, 1960. 38. Jagger, P. I., Block, J. B., and Burrows, B. A. Hepatic transport of Iissj Diodrasl. Clin. Res. 7:31, 1959. 39. Kaufman, J. J., and Hughes, D. Upright aortography: An aid to the stud) of renal artery stenosis. RodMogy 79:1017, 1902. 40. Kaufman, J. J., Schanche, A. and Maxwell, M. H. Excretory urography in the diagnosis of renovascular hypertension: Methods of enhancing its value. 7. Vrol. 09:498, 1963. 41. Kincaid-Smith, P. Vascular obstruction in chronic pyelonephritic kidneys and its relation to hypertension. Lancet 6903:1263, 1955. 42. Klapprotli, If. J., Takagi, H., and Corcoran, A. C. Segmental renal ischemic atrophy. Surger/ 46:1001, 1959. 43. Kohlsteadt, K. G., and Page, I. H. Liberation of renin by perfu«ion of kidneys following rcduclion of pul«e pressure. /. Exper. Med. 72:201, 1910. ‘1-1. KolR, W. J. Rc3;1521, 1958. 71. Poutasse, E. F., and Duslan, H. P. “Surgical treatment of renal hypertension.” In Moyer, J. (ed.). Hypertension: The first Hahne- mann sy/npos/um on hjpertenshe disease. Philadelphia: Saunders, 1959. 72. Poutasse. E. F., Duslan, If. P., and Pape, I. II. Surgical treatment of h) pertension due to renol ta«cular lesions. .1/. Clin. North America 45:179, 1961. Renovascular Hypertension 107 73. Rapoport, A. MoclificaRon of the Howard test for the detection of renal-artery ohstruclion. A'eitf England /. Med. 263:1159, 1960. 74. Revel!, S. T. R., Borges, F. J., Enlwisle, C., and Young, J. I). An appraisal of certain tests for the detection of hj-perlension of uni- lateral renal origin. Ann. Ini. Med. 53:970, 1960. 75. Schlegel, ]. U., Savlov, E. D., and Calior, F. Some studies in renal hypertension. /. Urol. 81:581, 1959, 76. Schmidl-Nielsen, B., and O’Dell, R. Interdependence ol urea and electrolytes in production of a concentrated urine. Am, J, Physiol. 200:1125, 1961. 77. Schroeder, E. Klinlska studies over nyrefunktionen hos iiephrec- tomerade. Diss. Kopenhamn (Danish), 19-14. 7C. Scott, R., Morris, G. C, Scott, F. B.. SeJrman, H. M., and Feste, J. R. The diagnostic approach to reno\ascu!ar hypertension. /. Urol. 86:31, 1961. 79. Serratto, M., Grayhack, J. T., and Earle, D. P. A clinical evaluation of the lo(Ioji) facet (Diodrasi) renogram. Arch. Jnt. Med. 103:851, 1959. 80. Smitli, II. W. Hypertension and urologic disease. Am. J, Med. 4:721, 1918. 81. Smith, H. W. Unilateral nephrectomy in hypertensive disea«e. J. Urol. 76:685, 1956. 82. Smith, P. G., Rush, T. W., and Evans, A. T. An evaluation of translumhar aortography. J, Urol. 65:911, 1951. 83. Spencer, F. C., Slaniej, T. A., Bafinson, ff. T., and Co/ien, A. Diagnosis and treatment of hypertension due to occlusive dl«ease of the renal artery. Ann. Surg. 151:674, 1961. 81. Slamey, T. A. The diagnosis of curable unilateral renal hyperten- sion by ureteral c.ill]etcrizalion. Postgrad. Metl. 29:496, 19GL 85. Slamey, T. A., Nudelman, I. J., Good, I*. Ih, Schwenlker, F. N., and Hendricks, F. Functional characteristics of renovascular hyperten- sion. Medicine -10:317, 1961. ion ADVANCES IN DIACNOSTIC UROLOGY 86. SUaflon, R. A., and Garcia, A. M. A clinical evalualion of ihe radioactive Diodrast renogram as a screening test in hypertension. Univ. AJichigari M. Bull. 25:260, 1959. 87. Sutton, D., Brunton, F. J., and Starer, F. Renal artery stenosis. Clm. Radio!. 12:80, 1961. 88. Taplin, G. V., Meredith, 0. M., Kade, 11., and Winter, C. C. Radio- isotope renogram: External test for individual kidney function and upper urinary tract patency. J. Lab. & Clin. Med. 48:886, 1956. 89. Toquini, A. G., Blaquiet, P., and Taquini, A. C., Jr. Studies on the renal humoral mechanism of chronic experimental hypertension. Circufalion 17-.672, 1958. 90. Tliotnpson, D. D., and Pitts, R. F. EiTects of alterations of renal arterial pressure on soilium and water excretion. Am, J. Phystol- 168:490, 1932. 91. Tobian, L Interrelationship of electrolytes, juxtaglomerular tells and hypertension. Phystd. Rev. 40:280, 19K). 92. Tobian, L, Thompson, J.. Twedt, 11., and Janecek, J. The granula- tion of juxtaglomerular cells in renal hypertension, desoxycoriicos- terone and past dexycorlito«lerone hypertension, adrenal regen- eration hypertension, and adrenal insuiTiciency. J, Chn. Invest. 37:660, 1958. 93. Tubian, L., Toumboulian, A., and Janecek, J. The effect of high perfusion pressures on the granulation of juxtaglomerular cells in an isolated kidney. J. Chn. Invest. .18:605, 1959. 94. Turgeon, C., and Sommers, S. C Juxtaglomerular cell counts and human hypertension. Am. J. Path. 38:227, 1961. 95. Ullrich, K. J., Kramer, K., and Doylan, J. W. Present knowleilge of the countercurrent system in the mammalian kidney. Prog. Cardlotas. Dis. 3:395, 1961, 96. Wilcofski, U. L., Whitley, J. E., Moschan, 1., and Painter, W. E. A method of parameters for the analysis of renal function by ex- ternal scintillation detector technic. Radiolog) 76:621, 1%I. 97. Wilson, C., ond Byrom, F. B. Hie vicious circle in chronic Bright’s disease: Experimental evidence from tlie h>l)er 1 en«ive rat. Quart. J. Med. 10:6.5, 1911. Renovascular Hypertension 109 98. Winter, C. C. A clinical study of new renal (unction test: The radioactive Biodrast renogram. J. Urol. 76:182, 1950. 99. Winter, C. C. Further experiences with llie radioisotope renogram. Am. J. Roentgenol. 82:862, 1959. 100. Winter, C. C., Maxwell, M. H., Rockney, R. E., and Kleeman, C. R. Results of the radioisotope renogram and comparison nitli other kidney tests among hypertensive persons. /. Urol. 82:674, 1959. 101. Winter, C. C., and Taplin, G. V. A clinical comparison and anal- ysis of radioactive Diodrast, Kypaque, Miokon, and Urokon reno- grams as tests of renal function. J. Urol. 79:573, 1958. 102. WoodrulT, II. W., and Malvin, R. L. Localization of renal contrast media excretion by slop flow anal)sis. /. Urol. frl:077, 1960. 103. Wylie, E. J., and Wellington, J. S. Hypertension caused by fibro- muscular hyperplasia of the renal arteries. Am. J. Surg. 100:183, 1900. 104. Yendt, L R., Kerr, W. K., Wilson, D. R., and Jaworkski, Z. F. The diagnosis and treatment of renal hypertension. Am. J. Med. 28:169, 1960. 105. Yuile, C. L. Obstructive lesions of the main renal artery in rela- tion to hj'pertcnslon. Am, J. M. Sc. 207:394, 1941, PERCUTANEOUS NEEDLE BIOPSY 6. OF THE KIDNEY TJie percutaneous needfe biopsy of ilie kidney lias become estab- lished as a relatively e/Teclive and safe method for making a pathologically correct diagnosis in diffuse diseases of die kidney. Because of the nature of the diseases for which the biopay is most useful, the procedure has been of most interest to physicians and pediatricians. The urologic surgeon is likely to become involved under two conditions: when a renal biopsy 3s desired and there is no one available with special experience in the procedure, and when complications develop which require surgical judgment and poasible surgical interv'ention. Altboiigh in research centers tlie majority of biopsies are Iwing performed by nonsurgical spe- cialists, it is probable (hat in the community they are being done by urologists. Percutaneous biopsy of the liver was made practical in 1939 by Iverseii and Uoholm,® vvlio introduced a special needle and technique for the procetiurc. Within a decade the procedure J/ecanie eslMhlieti a/jd the iuirwiuclwn of t}io YhiSthennsn needle hastened its acceptance in the United States. Perez Ara*” in 1950 publi'-hed a report on puncture biopsy of the kiilney which attracted little attention. However, in 1951 Iversen and Bruii' described a method of kidney hiopsy based on the prcviou«ly described technique of liver biopsy. In this technique the biop«y 110 Percvtancous Needle Biopsy of the Kidney 111 was taken with the patient in a sitting position, the kidney localized hy lead skin markers and roentgenograms in two dimensions, and aspiration performed Ly the Iversen-Roholm needle. The next year Ahvall" pul)Iished a report on 13 biopsies performed in 1944 using the Iversen-Roholm technique; he dis ncphrilU, and tuberculosis constitute rea«otial)Ie contraindications; Imncvcr, h would be dlfHcuU to observe pyelonephritis as a contra* indication in view of the great clinical inaccuracy of this diagnosis. Brun and Raaschou' found that of 62 patients with chronic pyelo- nephritis only 3.2 per cent developed a fever above 38 degrees centigrade subsequent to biopsy, whereas of 422 patients without chronic pyelonephritis 3.6 per cent devclojved such a fever. There was no evidence that the course of the dbease was in any way affected. Severe malignant hypertension has been proposed as a contraindication because of the increased risk of hemorrhage. Brun and Ranscliou^ al-o found that the incidence of gross hematuria was 12.5 per cent in patients vvitli hypertension as compared to 7.9 per cent in all cases, allhou}di on the day following biopsy the fre- quencies were 6.7 and 6.6 per cent respectively. Apparently there was no difference in the incidence of serious complications. In- creased venous pressure due to congestive lieart failure or possibly to renal vein thromhosj.s has also lieen suggested as a contraindica- Percutaneous Needle Biopsy of the Kidney 115 tion because of polenlial bleeding; lioirever, ibere are no data to support tbe risk under these circumstances. An agitated or unco- operative patient should not be subjected to a biopsy. On the other band, althougl 2 it is unlikely ll»at a basically uncooperative patient would give permission for the procedure, agitated patients can be adequately sedated or even anesthetized for tbe procedure, should it be indicated. Other contraindications mentioned by various au- thors are renal neoplasms, large cysts, renal artery aneurj'sms, and marked calcific arteriosclerosis. Tliere are undoubtedly many other relative contraindications wbicli require individual evaluation. t’REOPERATIVC ROUTI^E The patient is generally liospilalizcd for d8 hours suljsequent to die procedure. Laboratory examinations include liematocrit, bleed- ing, clotting, and prothrombin times, platelet count, serum creati- nine or blood urea nitrogen, and urinalysis. Tlie patient is typed and crossmatclied and one unit of blood is made available for im- mediate use. A satisfactory excretory urogram or, if renal function is inadequate, at least a scout film of the alidomcn with the patient in the lying position should be available. Tiiis is essential in order to determine the size and location of tbe kidney, as well as to be certain that there are two kidneys and that Loth are functioning. LUman*° believes that all children under eight years of age should he anesthetized, hut Kark and Miiehrcke” think that tliis depends to a great extent on the individual child. Vernier"” uses open biopsy on all cliildren under two year? of age. The procedure siiould be discussed witli each patient prior to the biopsy and lie should understand the risks involved as well as enough of the procedure to allow him to cooperate intelligently. The patient should liave no food prior to the procedure and lie may have mild sedation. We have found small amounts of meperidine 116 ADVANCES IN DIAGNOSTIC UnOLOCY helpful, altliougli otliers ihink. that the frequent narcotic-induced nausea negates any advantage. TECHNIQUE Equipment for a percutaneous needle biopsy would include the following: Roliolm-Itersen needle and locking syringe, or Franklin-Stlvcrman needle Mask Glo\ es 3-inch tape Disinfectant Procaine fiiops) specimen bottle 4 X 4-inch gauze flats Sandbag Crystal \iolet Tray trith: 2 cups for solutions 1 springe for anesthetic (2 or 5 ml.) 2 V^-inch 23-gauge needles 2 1%-inch 21-gauge needles 1 6-inch 22.gauge needle 1 Kelly forceps I knife handle 1 sliarp-puintcd blade 1 spinal sheet The I\ersen-Roholni needle measures 180 millimeters in length and has an external diameter of 1.9 millimeters. It has a pointed stylet and a ^ery sharp, slightly serrated edge. If the Iversen- Roholm needle is used, a special Record syringe is required which can he locked in any position h}' a ralclict. The Kark-Muehreke- Pirani technique recpiires a 6-iiich, 22-gauge exploring needle and a Franklin modification of llic Vim-SUvenuan needle.* Thc'C needles are made in 2Vi-iiicIi, 3’/i-incli, and 5®’i-iiich lengths. Tlie 3%-inch needle is the one which will he used in most instances; A\sitaWe from V. MeuUet i Ilaoorc Stwef. CliJeajso 12, tlL I'erculaneous Needle Biopsy of the Kidney 117 the short needle is used for children, and in rare instances the long needle is required for unusually ol>ese or muscular patients. Ivrraen’Roholm Technique Tile kidney is located by taping a lead mark over the approxi- mate site of the right kidney with the patient in the sitting position and by obtaijiing direct or retrograde pyelograms in two planes. The hack is then marked appropriately and the patient prepared with skin disinfection, local anesthesia, and a small skin incision for introduction of the needle. The needle is advanced almost to the anticipated deptlr of the kidney. At this point the stylet is removed, the syringe attached, and the piston pulled hack and secured to leave a suction within the lumen. Tlie needle is advanced 3 or 4 centimeters into the kidney and then withdrawn. When the tip of the needle comes out of the skin, the vacuum generally delivers the cylinder of renal tissue into the lumen of the syringe, from which it is transferred into the fixative solution. Kark‘MtteUrcke’Pirnni Technique Tliis technique was first described in 1954*“'^’ and further refinements were reported in 1958.'* The patient lies prone on a firm examining table or cart wiili his face turned to the left and with his arms over his head. A blood pressure cuff is placed on the arm and a nurse takes the pube and blood pressure periodically during the procedure. A long, 4-inch diameter sandbag is placed under the patient’s abdomen just below the costal margin; the purpose of the santihag is to compress the kidney against the hack and to limit its motion. The site of proposetl biopsy is marked on the roentgenogram and the distance of this point from the spinous process at the same level is determined, as is the distance from the lateral border of the kidney to the spinous process. Cr)'stal violet is used to draw on the palicnl’s back a line connecting the spinous processes and two parallel lines at the distance from the i::u ADVANCES IN DIAGNOSTIC UKOLOCY breath, the stylet is icmoved, and llie cutting blades arc inserted and pushed to their full depth. Then, without advancing the cutting blades the outer sheath is pushed over and slightly beyond them. The needle and sheath are then withdrawn and tlie patient i« instructed to hieathe. Figures 1 and 2 illustrate the anatomic relationships in needle biopsy of the kidney. Wlien the biopsy has been successful, a small core of tissue measuring 1 to 2 centimeters hy 1 millimeter will have been obtained {Fig. 3). This tissue will immediately sink on insertion into a fixing fluid, whereas fatly tissue will float. Not infrequently the needle will be removed and no tissue will he found. This may be a result of failure to locate and fix the needle in the renal parenchyma or of failure to make a cut when Figure 3. Typical renal Iiiopsy (low and higli power) showing amount of tissue available for diagnosis. the needle is in the kidney. Bolli of these causes of failure should decrease with experience. There seems to be very little increase in the risk of the procedure if sc\eral aspiration attempts are made before a piece of tissue is obtained. In fact, some authors have taken an extra core of tissue for electron microscopy or culture in addition to the specimen taken for light microscopy. It is probable that success can he increased by the use of a relatively new needle, because the blades may become slightly sprung and thus interfere with proper cutting of the tissue. It is important that the needle not be too deep in the kidney at Uic time the cutting blades are 122 ADVANCES IN DIAGNOSTIC UKOLOCY inserted, for in ll\is circumstance medulla may be obtained without cortex. On the oilier hand, if the outer slieatli js not uell embedded in the kidney parenchyma, advancing tlie cutting blades may force the kidney off the sheath, and no tissue may be obtained at all. After the tissue has been obtained, several 4 X d-iticli gauzes are placed over the puncture site and the entire area is compressed by broad strips of tightly applied adhesive. The patient remains on the sandbag for 30 minutes so that some degree of tamponade is maintained between the sandbag and llie pressure dressing. Because of tbe discomfort producee initiated. At least i\so of the Tcporled dcallis could liave been avoided had llie presently established contraindications been recogiiizctl at the time that the liiopsies were performed. Another patient may have been saved by more ap- gre«sive antiliypolensivc therapy. Some complications in percu- taneous kidney biopsy arc probably unavoidable, althougb in rompeleni bands the risk of accidental death seems quite small. The available data sugge>l that death owing to biopsy occurs in less tlian 0.1 per cent of patient®. Compliralions KegwWwg Opemtirt' Inlrrrcnlion Kark and associates’* reported no case requiring operative inlcn-enlion in the first 500 biopsies, llrun and Raa«rliou'* reporletl Percutaneous Needle Biopsy of the Kidney 127 one patient in whom a hemodialysis became imperative as a consequence of llie rise of serum potassium to 7.6 milliequivalents per liter within 24 hours after a biopsy. After 3 hours of dialysis the patient developed a steady hematuria, and a right nephrectomy was required to control the bleeding. During the period of opera* tion and hematuria, 50 transfusions of 500 milliliters of blood were given. The postoperative course was uncomplicated and the patient recovered from both the nephrectomy and the acute renal failure. Examination of tlie excised kidney revealed a fistula between the renal arler)’ and the renal pelvis, undoubtedly tiie result of tile biopsy procedure. We have had a similar complica- tion in our series. A liiopsy was taken without complications except for the usual microscopic Iicmaturia. But when the patient started to amhulate, lie developed gross hematuria. He was returned to bed rest and the hematuria subsided, only to recur each time he began to ambulate. After several months the hematuria disap- peared and lie was discliargcd. However, lie was found to Iiave a gradually progressive Iiypcrtension wliicli became associated with eyeground changes. Intravenous pyelograms revealed an absence of function in the riglit kidney. A neplirectomy was performed, with subsequent cure of the palienl's hypertension. Tliere ivas nearly total occlusion of the arterial lumen, and it was inferred that this was the mechanism I»y which the hematuria was originally cured. Schreiner and Berman"* report 2 instances of operative inter- vention in 150 biopsies. In the first a left renal biopsy was per- formed on a patient with sickle cell disease. During the procedure the tip of the spleen w'as nicked and slow bleeding persisted for more than 24 hours. As a result, the .scheduled splenectomy was advanced ami the spleen was removed uneventfully. In the second instance the exploring needle apparently tore a renal vein and a large perirenal hematoma fonnerl. At operation the hematoma W'as evacuated, the vein was ligated, and again the patient made an uneventful recover}*. 128 A.DVANGRS IN DIAGNOSTIC UROLOGY Felton and Andronaco® iiave reported a serious delayed Jiemor- rhage wliidi occurred 9 days after an oUier\vjy Yamauclji and associates.®^ Thc«e authors postulated that the nephrotic syndrome is often associated with a low blood volume and that in such cases 130 ADVANCES IN DIAGNOSTIC UROLOCV tlie SOO-milliliter blood loss may have been sufficient to produce irreversible «bock. They subsequently conducted studies to de- termine the blood volume in 30 patients with various forms of nepl»iQ«is. Tiiey found that in 18 patients l!ie blood volume ranged from —10 to +36 per cent of the prcrlicted volume. Ho\ve\er, tl was 12 to 15 per cent below prediction in 6 patients, 22 per cent below in 2 patients, ami 35 to 43 per cent below predicted values in tlie remaining 4 patients. Tbe inveMigalors thought that in these 4 patients a further slight decrease in blood volume might be sufficient to cause shock. They advised that, prior to biopsy, blood volume determinations be made of all patients will* ne- phrosis, and that where indicated the blood volume be increased toward the normal value. We have had one rather unusual e.xpcrience with shock during the performance of a biopsy. The patient was a 51-year-old lawyer who had had a myocardial infarction approximately 10 years previously and w'as subsequently found to have a rather high serum cliolesterol. Proteinuria was not noted until u few months heforc the ]iia[i»y attempt, at which time a mih) amount of ankle and leg edema w'as noted. At the time of hiop^y the patient had an elevated serum cholesterol, a deprc«'ed serum nlhiimin, and marked proteinuria, aUhoiigli he appeared well and there was no visil>le edema, lie wa« placcal. clinical, funclional and morphological studies of rates of healing and progression to chronicily. Medicine 10:20.3, 1961. 11. I.atrala1iti, J. Experimental studies on the innuence ol certain hor- mones on the deiclopnieut of amyloidosis. Acta endocrinol. Suppl 16, 1953. 15. Litnian, X. N., Vuile, C. L., I.alta. If., Cllcklicli. D., and Smith, F. C . Jr. A critical evaluation of renal biopsy in children. A.M.AJ. Dh. Child. 102:.321, 1901. 16. Muchreke, R. C., Kark, R. M- and Pirani, C. !>. BIop«y of the kid- ney in the diagno«is and mar>apemcnt of renal dl«e3«c. Sew England J. .Med. 2.33:537, 19.35. 17. Muchreke, R. C., Kark, R. M., and Pirani, C. L. Ti-chniquc of per- cutaneous renal biojwy in the prone position. J. Urol. 71:267, 195.3. Percutaneous Needle Biopsy of the Kidney 135 18. Parrisli, A. E., and Hoive, J. S. IVeetHc biopsy as aid in diagnosis of renal disease. J. Lab. & Clin. hied. 42:152, 1953, 19. Parrish, A. E., and Houe, J. S. Kidney biopsy: A revicH’ of one hundred successful needle biopsies. Arch. Jnt. Med. 96:712, 1955. 20. Perez Ara, A. La biopsia punctural del rinon no megalico consider- aciones gencrales y aportacion de un nuevo metodo. liol. Liga contra el edneer 23:121, 1950. (Quoted by Refs. 3, 11.) 21. PliilUppi, P. Robinson, R. R., and Langelier, P. R. Percutaneous renal biopsy : Obsen'ations with special reference to asymptomatic proteinuria. A.M.A. Arch. Int. Med. 108:739, 1961. 22. Ucubi, F. La ponclion-biopsie du rein. Ilelvet. chir. acta 21:128, 1954. 23. Sala, A. M. Value of renal biopsy determined by autopsy control. Presented at 3rd Internal. Cong. Clin. Path., Brussels, 1957. 24. Schwiebinger, C. W., and lloriges, C V. Aspirolion biopsy of the kidney. J.AM.A. 154:1198, 1955. 25. Schreiner, G. E., and Berman, L. B. Experience Avith 150 consecu* tive renal biopsies. South. M. J. 50:733, 1957. 26. Vernier, R. L., Farquliar, M. G., Brunson. J. G., and Good, R. A. Chronic renal disease in children. A.M.AJ. Dis. CAiW. 96:306, 1958. 27. Yamauchi, H., Hopper, J.. Jr., McCormack, K., and Lambert, K. Hypovolemia in the nephrotic syndrome — a contraindication to renal biopsy. jVcw England J. Med. 263:1012, 1960. 28. Zelman, S. Fatal liemorrhage following ncetlle biopsy in uremia: Report of a case. JuiALA. 154:997, 1954. Additional Refeeences 29. Rapoport, M. Discussion of paper by Haas, E., and Goldblatt, H. ‘‘Role of the renin system in experimental hypertension.” In Mel- coff, J. fed.), Angiotensin Systems and Experimental Renal Diseases. Boston: Little, Bronn and Company, 1903. 30. Wolstenholme, G. E. W., and Cameron, M. P. (eds.). Ciba FounJa-^ tion sympoitum on renal fitopsy; Clinical and Pat/io/ogico/ Signifi- cance. Boston; Little, Brown and Company, 1962. 7. DIAGNOSIS OF PROSTATIC CARCINOMA CLARENCE V. HODGES Pro^lalic cancer w llie moefore 30% reduction) 360 degrees and withdrawn. Tlie needle is reiiilroduccd unlil 3 or 4 good cores of tissue (Fig. 1) have l)een olilaiued from the suspicious area and front (he opposiie lohe as uell. The procedure may iie facilitated, if desiresy, either perineal or traits* rectal, for those patients wilh inoperable legions in nbom a histologic diagnosis is necessary prior to initiation of endocrine therapy. A positive diagnoals of malignancy is occasionally obtained from the tissue cureltings from transuielhral proi-talectomy. This method is not utilized in early cases bccau.talc glaiwl by estimation of lhi'‘ fraction. Subse- quently Bonner and associate^* administered le-loalcrone to pa- tients with a questionable diagnu-^is of pro'-lalic cancer, Imping to accentuate otherwise normal ImeN of “]>rostalir” scrum acid pIio*.phata«c by stimulation of the tumor growlb. Siiliscijucnt in- vestigators'* have not been able to sub^tuntiatc tins hope. At the Diagnosis of Prostatic Carcinoma 141 present lime there is no serum enzyme test I’ROSTATIf: EANr.IIR About 80 per cent of patients with disseminated prostatic cancer show an elevation of the scrum acid phosphata«e aho>e 10 King-Armslrong units £>cr 100 milliliters of serum. iS'onnal range for this test lies liclow 5 units, and the range iwtwccn 5 Diagnosis of Proslatic Carcinoma I‘13 and 10 units is considered suggestive of disseminated prostatic cancer. The normal range for Bodansky or Gutman units is 0.5 to 2.0. Wiilj a few rare ext^plions, elevation of acid phosphatase above 10 King-Armstrong units may Ije considered diagnostic of proslatic cancer. Elevation of the serum alkaline phosphatase activity above 13 King-Armslrong tinits, 4.5 Bodansky unit**, or 10 Gutman units is a reflection of the increased bony activity secondary to metaslases. Similar elevation is seen in other types of osseous disease as Avell as in liver disea«e, and is therefore not particularly helpful diagnostically. A word of caution should l)e expressed regarding the effect of rectal palpation of the prostate gland on the level of serum acid phosphatase. Moderate elevations of the serum acid phosphatase may occur as a result of examination of the prostate through the rectum and may persist for 24 hours. Serum acid phospliatase detenninations may thus he inaccurate during this period. In roentgenograms of the pelvis, lumbar spine, and upper femora, the characteristically blotchy, moth-eaten osteoblastic lesions (Fig. 2) suggest the likeliliood of disseminated prostatic cancer. These lesions tend to condense and then disappear in a favorable response to endocrine tljerapy. Other common sites of liony involvement are the ril»s and scapula. Involvement of the inguinal or supraclavicular nodes is frequent enough to suggest the possibility of prostatic cancer in the elderly male, and the finding of a mass in one of tlieone disease will occasionally suggest the likelihood of prostatic cancer. Such cases should be documented by biopsy of tlie primary site. AD\’ANCES IN DIAGNOSTIC UROLOCV lU Figure 2. nocntgenogrom o( tlic pelt is aR<) lumbar spine sbotting ctiArac> leri*tic o$teobla*lic Icsinns of niela«l«tic proslstic enreinomn. 5 U M M A It V Early pro«tatic cancers amcnalile lo surgical removal arc diagnosed by open periiiej] biopsy. Inoperable lesions may be diagnosed readily by tninsperincal or tran«rcclal needle biopsy. I)i«scmmalecl proviatic cancer \s fuitbcr documenled by clctalcd serum acid pliospbatase and llic deinonslralion of rbaracteri'tic lesions on roenIgenogram«. Every legion suspected of being pro** latlc cancer must !«? documenled by bistologlc evidence l>efore definitive llierapy is itnlfaU>d. Diagnosis of Proslatic Carcinoma 145 REFEKENCES 1. Bonner, C. D., Homburger, Smith, G. B., and Borges, P. R. F. Prostatic serum add phosphatase level In cancer of the prostate. JAMA. 1&1:1070, 1937. 2. Clarke, B. G., Leadhetter, W. F., and Campbell, J, S. Implantation of cancer of the prostate in site of perineal needle biopsy: Report of a case. /. Urol. 70:937, 1953. 3. Culp, D. A., Flocks, R. H., and Poito, J. R. Retropubic biopsy of the prostate. }. Urol. 79:873, 1958. 4. Dahlen, C. P., and Goodwin, W. E. Sexual potency after perineal biopsy. J. Urol. 77:600, 1957. 5. Daves, J. A., Tomskey, G. C, and Cohen, A. E. Transrectal needle biopsy of the prostate. /. Urol. 83:180, 1961. 6. Emanuel, M., and Foote, E. L Transrectal needle biopsy in the diag- nosis of prostatic carcinoma. }. Maine M.A. 40:231-, 1957. 7. Ffnkle, A. L., and Mojers, T. G. Sexual potency in aging mates; V, coital ability following oiien perineal proslatic biopsy. /. Vtol. 81:C-19, 1960. H Fisbman, W. JI., Dart, R. M-, Bonner, C. D., Lcadbetter, W. F., Lerncr, F., and Iloniburger, F. TJie new meihm] for estimating serum acid phosphatase of proslatic origin applied to the clinical investigation of cancer of the prostate. J. Clin. Invest. 32:1031, 1953. 9. Goodwin, W. E. Radical proslaleclomy after previous prostatic surgery. JA.MA. 148:799, 1952. 10. Goldman, E. J., and Samellas, W. Local extension of carcinoma of the prostate following neetlle biopsy. /, Urol. Bt:575, 1960. 11. Grabstald, H. Further experience vrilh transrectal biopsy of the prostate. /. f/roL 7 V:211, 1955. 12. Hudson, P. B., Finkle, A. L., Hopkins, J. A., Sproul, E. E., and Stout, A. V. Proslatic cancer XL Early prostatic cancer diagnosed by arbi- trary open jverineal biopsy among 300 unselecled patients. Cancer 7:690, 19S1. 116 ADVA N CCS IN DIAGNOSTIC UnOLOCY 13. Kaufman, J. J., Rosenrtjal, M., and Goodwin, W. E. Diagnosis of prostalic carcinoma./. £/ro/. 72:150, 1951. 14. Kaufman, J. J., and Schultz, J. I. Needle biopsy of the prostate: A reevaluation. /. Vroi, S7:164, 1962. 15. Nobles, E. Tl., Ir.> Kerr, W. S., Jr., OutoU, C. II., and Routke, G. M. Serum prostatic acid phosphatase leiels in patients with carcinoma of the prostate. /.A.jU./!. 161:2020, 1957, 16. Parry, W. L., and Finelli, A. F. Riopsy «f prostate. /. Vrol. 81:613, 1060. 17. Peck, S. Needle hiopsy of the prostate. /. Urol. 83:176, 1060. 18. Smith, D. 11. General urology, eA. 3 Los Altos, Calif,: I,angc Medical Puhlications, 1961. DIAGNOSIS OF 8 . ADRENAL H YP E R FU N CT I O N FHANK H IN MAN, JR., AND HOWARD L. STKINDACll ADRENAL CORTICAL I! Y P E R F U N C T I 0 N DifTerenliation of adrenocortical disorders mnst be made in two paran;eters, iJie hormonal and the anatomic. The first is as* sessed by measurement of excretion of various metabolites, with or witiiout adrenal stimulation or suppression; the second is evaluated by radiograpliy. When the two are combined, the differ- entiation permitted by them establishes the diagnosis and allows intelligent treatment'^ (fig* 1)* The three principal liormonal products of the adrenal cortex are cortisone, androgens, and aldosterone; the excessive produc- tion of these hormones produces Cushing’s syndrome, virilism, and primary aldosteronism respectively, llytlrocortisonc Hypersecretion (Cushing's Syndrome) Hj-perfunclion of the adrenal cortex, tlie excessive release of corticoids, produces a familiar clinical picture (Fig. 2). Labora- lor)' tests may sbo^v• decreased numbers of eosinophils and lympho- cytes in the circulating hloovith Cusliing’s syndrome this ratio remains elevated as the weight of the patient increases (Fig, 3). If tlie 24diour excretion of 17-hydroxycortj- coids is more tlian 0.070 milligrams per pound, Cushing’s syn- drome is present by calculation of the ratio IT-OH/body iveight. Hormonal differentiation: Iij'i^erplasia-adenoma vs. carcinoma. The interaction between the pituitary and the adrenal glands is shown in Figure 4. Normally the administration of ACTHJ will stimulate increased 17-hydroxycorticoid (and 17-ketosteroid) ex- • Endocrine and metabolic atudies werr r*rn«t ««{ by Dr. Peter II. Forgham and associates at tlie .Metabolic lioearch Unit, University of Caliiornia School of Mcdi- tine, San Francisco. t in some laboratories 17*kctogenic aieroiili (IT-KCS) ore utilized instead ot 17- bydroxycorticoids {17-011) because the chemical determination is easier: Determine IT-Vctosteroids (17-KS), convert 17-011 to IT-KS, again determine 17-KS; the diDer- ence is the 17-l.eiogcnic steroid level. t Tiic standard ACTlI stimulation lest is performed by giving 20 units of ACTIf by sJotr intravenous drip over an 8-boor perimL Urine h collected for 17-byt««5 Mocks corti- sone production, and llic resulting uninhihited piluilar) secretion increases adrenal function to make mcrca*ing amounts of Compound S, which can l>e measured in the urine a* I7-ketogenic sleroids. Diagnosis of Adrenal Ilyperfunction 151 crelion from the hyperplastic and adenomatous adrenal gland, the cells of which are still somewhat under the control of tlie pituitary gland. Carcinoma of the adrenal gland, on the contrary, is autono- mous; no rise in excretion occurs with ACTH administration. In 19 cases of hyperplasia proved by operation, we found that the mean iiasal level of IT-hydroxycorticoids was 21.1 milligrams of 17-hydroxycorticoi(ls in 24 hours, 3 times the average normal level. ACTH stimulation produced a 3-fold increase to 66.3. Similar results were obtained in 5 cases of adenoma, in which the basal level vias 21.7 miJligrams of 17-hydroxycorticoids in 24 hours and ro«e to 79.3 after ACTH siimulation. Tiie 3 patients with carcinoma, on the other hand, had a liigher average basal level (36.9 mg. 17-0H/24 hours) hut shon-ed no appreciable rise (only 6 per cent) after ACTH administration, thereby demonstrat* ing autonomy. Tliis finding was true of the indindual levels as well as of the average level of the 3 patients. Similar findings have been oliservec! with 17-ketoslcroiU excretion. These studies indicate the reliability of the ACTH siimulation lest in differentiat- ing carcinoma from liyperplasia and adenoma (Fig. 5). ACTH from the pituitary gland stimulates corticoid production, wliich in turn suppresses ACTH production. Administration of corticoids will similarly suppress pituitarj' ACTH production. If TOTAL CASES CORRECTLY OtAGNOSEO EQUIV- OCAL ERROR HYPERPLASIA OR ADENOMA ZA o CARCINOMA 3 5 O o x(a4&4c levec n OM/g4 hr*i ^sr-5T4MvtATio// levet'. t/Omy /7 Figure 5. neliahilitj* of ACTfl stimulation test to identify carcinoma {27 cases, surgically verified). 152 ADVANCES IN DIAGNOSTIC UROLOGY tlie adrenal tissue is still tinder piluitar)' control, tlic resulting decrease in ACTH stimulation will produce a decrease in corljcoid excretion, as measured by ITdiydroxycorticoid levels in tlie urine {as in normal, liyperpla^tic, and adenomatous adrenal glands). If tlie adrenal tissue is autonomous, as witb adrenal carcinoma, the administration of corticoids will not alTect the excretion of liydroxycorlicoids by tbe tumor, 9-a-Fluorobydrocortisone^ or preferably dexamelhasone,* po- tent glucocorticoids, act in a way parallel to endogenous hydro- cortisone to suppress pituitarj- excretion of ACTH and so mcas- uiably reduce the output of adrenal IT-hydroxycorlicoids. Wc have used these substances in virtually all of our cases with results that supplement tl\o«c from the stimulation lest, llouever, we have ob«er\cd Uiat the ACTH tost is more reliable, more apt to he uncquuQcal, and lieucc more useful clinically. To complete this discussion on regubiling agent®, rcforcnco must be made to SU-1885 (Melopirone).*® This suhstanoe blocks ll*;fl-hydroxylation, which Is necesion of l]-de«oxyhydrocortisone to hydrocortisone in the adrenal. The fall in production of li)drocorlisonc stimulates ACTH production by the pituitary (see Fig. 4), which in turn causes secretion of increased amounts of the hiologically inert substance, ll-dc«oxy- hydrocortisone. This suhsloiicc i- nie.isure(l as 17-fcetogcnic steroids in the urine. At the Unirersity of California Medical Center 10 of the 37 patients with Cushing's syndrome have lieen studied with SLMBOj to dilTerentiate hyperjilasia from tumor.’'* Six patients with hyper- plasia showed signincanlly merea«esil)ilily after anotlicr. Only hyperplasia reaj)onds to all test suhstaiiccs; carcinoma rc'^pomls to none. Iladiograpliic (litTcrciiiialioMt liyperptosia te. a(lcn»mn>cnr(-i> noma. We lia\e shown llul hormonal tests separate the catch Momi.s from tlie other two lesions producing Cushing's sjmdrome. We slmll now itidicate how roenlgcnograpliy not only dKTeren* liales hyperplasia from tumors of the adrenal, hut more impot* tatilly iiow it localizes tl>e lesion for the most advantageous surgical attack. In patients properly prepared but free of adrenal disease, plain roentgenograms of the alHlomcii often show small triangular or semilunar shadows ootlinerl hy the less dense pertadrennl fat. A large tumor may show' displaonnenl of llie siomacli. Tomography may allow lictter discernment of the adrenal margins; too often, however, the contrast hctwccii adrenal suhstanee nn normally lies lower than the right in 15 per cent of cases. In some <-usej. the adenoma is cxtm-adrcnal. Retrograde pyelograms are of e%en less help than mira\enous urograms. f\oi1ogra]>liy may he of u«e in meilidlar)' (hy|Jen'asculur) neoplasm (m'c Adrenal Diagnosis of Adrenal Hyperfunction 155 Figure 9. Lefl renal displaceinenl anil ro!a!ion I)> large aJrenal adenoma. Note cliange in renal axis. Medullary Hyperiunclion, p. 176), bul it is le*s often lielpful in identifying masses in (he adrenal cortex. Relroperiloneal pneumography is by far the most valuable pro- cedure for differentiating luiiior from hyperplasia and for localiz- ing the tumor. Two techniques are acceptable. In one a spinal needle is introduced presacrally and its lip is placed just heneatli the rectal wall as the patient lies on his right side (Fig. 10) The patient i« turned on his left side for the second part of the in- sulation. About 500 cubic centimelew of oxygen for each side is introduced under the control of water displacement. No fatalities have heen reported when this technique has been followed in 156 ADVANCES IN PI AGNOSTIC UnOLOCY Fif^ure 10. Intro(fuctlon of fipinal needle into relropcrilonca! spare l>) advancing it to lamina propria of rectum above ibc spiiinciers. detail, but since oxygen is slowly al>«orljcd, there is always the danger of gas cmlvoUsm. If gas cmbolKm is suspected, the patient should he rolled back onto Ids righi side. In the other Jechiuque, developed by Landes and Ran«oin,*’ carbon dioxide, which is alisorlied almost ns rapidly as it is in* jeeted, is u«ed. I5ccau«c of its rapid absorption, this gas must be instilled at almost the exact lime that the radiographic exposure is made. For this simultaneous proredure, two small polyethylene lulips rmivt he introduced tliroiigli needles into the retrorectal space. The patient is then placed upright hefore the radlognipliie npp.iralus and the carbon dinxidc is iiijerted ihrotigh the fnx' ends of tlie tubing. Allhoiigli this Icclmique is more dtfllcult and Diagnosis of Adrenal Ilyperjunction 15 < ihe roentgenograpliic results are less uniformly satisfactory, its unquestioned safety may Avarrant its Avider use. The gas outlines the normal adrenal glands Avithin Gerota’s fascia, Avhich forms a sloping margin concave over the adrenal and convex over the upper lateral surface of the kidney (Fig. 11). It is of greatest importance to identify Geroia’s fascia every time this teclinique is used, since any mass lying superior or lateral to it lies outside the retroperitoneal space. Within Gerola’s fascia lies the loose-structured perirenal fat, Avldch is readily dissected from the kidney and adrenal l»y the rising gas. This may alloAv the kidney to fall domnvard, array from the adrenal gland, and to rotate on its vertical axis. GEnOTA’S FASaA Figure il. Normal right adrenal ilemon«lraled by presacral ga<} in- suHlalion, showing fa«wia of Ccrota ami adrenal gland (heavy arrows). 158 ADVANCES IN DIAGNOSTIC UtlOLOCY /'ijiHfe 12. Bilatcrat Ii)pcTpla*ja. \ 4 ) Witli ga« insufflation nlonr. f®' about left adrenal i.»b*curw drlail; drimcalion is al«o jtoor on llic ngbl- (8) 'ft'illi tomogrqpby, the adrenal outlines ma> }>e wm. Adrenals ma) api>ear ol normal «r s<»nje«hat enlarged size in adrenal li)por{iln«ia pro* during Cudiing's sj ndromc. Diagnosis of Adrenal llyperfunction 159 When normal, holh adrenaU appear most commonly as tri- angular shadows somewhat overlapping the upper margin of the kidney; these shadows may appear long and slender as if flattened out over the kidney. We found that the average area exposed by pneumograpliy measures 4.2 square centimeters, altiiough it ranges from 2.0 to 8.7 square centimeters.'* At our institution Holmes and associates*® found at .autopsy tJiat there is also a wide range in wciglils of adrenal glands, and that the weight of a gland is roughly related to the weight of the patient. In adrenal cortical hyperplasia the exact margins of the adrenal cortex are dilTicult to trace because the increase in fat produces a markedly reticulated, indefinite shadow (Fig. 12). In addition, the correlation between size and function is poor (r = 0.123), although a trend is apparent wlien weiglit and function after ACTH stimulation are plotted (Fig.-13). Consequently the hormonal tests must lie relied upon to differentiate the liyperplastic gland WCICHT, DOTH Figure 13. Uflation of adrenal wdght to function after ACTH stimulation in ]G cas lies u'ilhin Gerota's fascia (and is therefore perirenal) or lies outside Gerota’s fascia (and is therefore not adrenal). In one case where plain films indicated Figure 14. (/t) Lack ol drtmcntion of adrenal adenoma on inlraicnous urogram. (/?) Hounded mas^ acen !>)' pre*acral gas in*unialii>n. 762 A D A N C E S IN D I A C N O S T I C UR O L O C Y nn ndrerial tumor, gas studies shmted Utat the mass lay outside tlie fascia arid operation disclosed a pancreatic cyst (Fig. 15). A virilizing tumor merely produces excessive amounts of andro- gens; it does not suppress the piluitar)' production of ACTH and therefore does not cause contralateral adrenal atrophy. A tumor causing Cushing’s syndrome, on llm contrary, is always accom- panied hy contralateral atrophy (Fig- 16); thus the hlentificallon of such atrophy is a valtiahle diagnostic aid. If both adrenals arc small 1))’ pneumography, nn extra-adrenal tumor may he su-pecicd. In one of our cases, exploration of one /lank proved the presence of adrenal atrophy and nn adrenal rest tumor was suhsequenlly removc Ino much ga«. (/?) Belief delineation in a later film. he a«sociate Uelalion of site of sella to hyperplasia and tumor in 23 cases of Cushing’s syndrome. prolonged remission in as many as lialf of the patients treated. It may lie used either primarily or after diagnostic unilateral adrenalectomy. The efTectiveness of pituitary irradiation will be determined by the remission of the symptoms due to llie presence of excessive corlicoids. It can l>e measured quantitatively by ad* ministration of SU-4885; patients with adequate pituitaiy destruc- tion will show a much reduced response in contrast to the increased excretion of 17*kelogenic steroids occurring before irradiation. However, in most cases the effects of radiation arc slow and re- missions by x-ray Q]onc are less tbaii 30 per cent. Total excision of lioth adrenal glands assures cure of Cushing's syndrome, hut it requires lifelong and potentially hazardous replacement therapy, and also may result in increased incidence of pituitary tumors. However, if subtotal excision is performed, recurrence appears in about 30 per cent of patients. If it were possible to select those patients in whom subtotal adrenalectomy would be adequate, total removal could be re«ervcd for the re- mainder (particularly younger patients with severe, rapidly pro- gressive disease). The 20-uiiit ACTH te'st may lielp differentiate the former cases since it forces maximal function from the adrenal cortex. The level of potential function can llierefore be ascertained from both glands preoperatively and from the remaining gland after unilateral adrenalectomy (Fig. 21). If the po'^topcralive level of 17-hydroxycortico?ds after ACTH stimulation is half or IhjnTjiIasI Diagnosis of Adrenal Jiyperfunction 167 ACTH STIMULATION TEST •ir TOTAL ftlCHT AORENALECTOMT ACTH SriMi/LATIOW TEST TOTAL LEFT SUBTOTAL LEFT AORENALECTOMT ADRENALECTOMY Figure 21. Steps in determining need for total versus partial adrenal- ectomy. less than tliat before operation, this is evidence that tiie remaining gland will not continue to hypertrophy. Hence four-fifths of the remaining gland may he removed with reasonable expectation that normal lionnonal levels will be retained- If, on the contrary, the postoperative level after unilateral operation approaches that before operation, total excision is performed. In six out of eight patients witli Cushing’s syndrome due to liyperplusia studied at the University of California Medical Center the poshtimulatron corticoid level, measured for periods of from one month to up to two years after unilateral adrenalectomy, remained lialf that of the preoperative level.*' Tlie other two patients showed a rapid return to preoperative levels and required total adrenal- ectomy. Replacement therapy is started at the time of operation willi a dose of 100 milligrams of hydrocortisone administered intra- muscularly. (It is not necessary to start earlier since the effects of llie liypersecretion of the hyperplastic adrenals will continue at least six hours after extirpation.) Fifty milligrams are given in divided doses for a day, and then the quantity is reduced to a maintenance dose of perhaps 25 milligrams of hydrocortisone per day. The result of surgical treatment of bilateral hyperplasia is permanent remission in from 80 to 90 per cent of all cases. In some patients subtotal adrenalectomy is followed by recurrence 168 ADVANCES IN' DIAGNOSTIC UnOLOCY (or peisislcnce) of symptoms; In such ca«e« total adrenalectomy is subsequently performed. Treatment of unilateral adrenal tumor. The great advantage of preoperatite radiologic localir^lion of the adenoma or car- cinoma is that an attack through the most direct and clo-cst surgical approach, the flank, is made po-sihle. In almost all cases an extrapleural apjiroach hy excision of the eleventh rib lirings the surgeon directly to the m3«s. The superior margin of the tumor, as it is pulled donn hy traction on the kidney, may he freed under direct vision. The many small ^c^«els are individually clam]>cd, transected, and ligalei! (or clipped if they are very small), and flie larger adrenal vein it divided and ligated. Trenlmcnl of nicttt«lntic adrenal rnrrinoma. Although uc have had little experience with ortho-paraprime DDD in the treatment of advanced adrenal cortical carcinoma, researchers at the I^ntional Cancer Institute' }ia\e obtained sustained remissions in jiatienls who could tolerate the drug. The lack of response to ACl'H stimulation shoued that c%cn the normal adrenal lia-'tu' >\a5 completely suppressed. lh and voice clmngc develop precociou-ly from the excessive androgen secretion (Fig. 22). Adrenal in«ufiicicncy, caused !)y fatilly cortisone j»rothiclion d\je to a congenital ali- sence of certain enx>mes» is a prominent feature in certain patients. Tlie lahorator)’ findings arc tlio«c of increased 17‘keto«tcroid excretion. In one 3l'^->ear-old patient for example, the exerelion of ]7-kcto«feroids was 25.9 millignitn< in 21 hours. Pregnanediol and prcgnarielrioJ were specifically elevated in tlic nrlnc. The crucial lest for (lifTerefitialing this form of iiitersexuality from other forms i« the response to the adminlslraiion of cortisone, nhich will caucar-olil girl congenital adirnal h>p»T}*}a«ia. suppress. figure 23 . DifTerentialion of hyperplasia, adenoma, and carcinoma in adrenal virilization. 172 ADVANCES IN DtAC NOSTIC UR01-OC\' In brief, diagnosis re^fs on (1) e^tnIJIi’*ll^ng “female” genetic sex Iiy eliromalin sludie«, (2) noting intersexnal genitalia, (3) observing progressive masciiliniration in secondar)* sex clurac- leristics, (4) finding elevated 17-kelostcToids, and (5) causing their return to normal with coriisuiie, thereby producing a clinical remission. Since surgical inlcrvention no longer plays a role in ibis disorder (except for revision of llie external genitalia), radiograpbic visualization of the adrenal glands is unneccssaiy. Acquired virilization shows elevated 1 7*keloslcroid excretion whicii will not he suppressed if it i» due to adenoma or carcinoma. The main diffcrcnlinlion and, more im|)(>rtanlly, the localization will be indicated by radiography. Itnenlgcnograpldc difTerentiation. Only in tllC acquired form' of androgenic hypersecretion will radiographic leclmujucs be necdcjl. Here the problems arc exactly those of Cushing’s syn- drome, except that tlic tumors arc often larger and may even be Figure 24. Hablluf and gmilslia in unlrealK] adrenal liyperjilasia. Diagnosis of Adrenal Hyperfunction 173 palpable. Tlie flow chart shown in Figure 23 has proved useful in the diagnosis of tlie several forms of androgenic adrenal hyper- function. Treatment. Without treatment, androgenic hypersecretion re- sults in extreme virilization (Fig. 24). Cortisone or its analogues will effectively suppress hyperplasia, hut excision, by the same approaches used for other adrenal tumors, is required for all other cases. Since the pituitary gland is not suppressed by the excessive androgen secretion, the contralateral gland is not atrophic, and supportive therapy is not retiuired during or after operation. Aldosterone Hypersecretion (Primary Aldosteronism) The syndrome of excess secretion of the salt-controlling hormone of the adrenal cortex, aldosterone, was recognized in 1955.® Tiie disorder is probably more common tiian would be assumed from the number of cases reported. Diflferentialion is achieved princi- pally by endocrinologic means (Table 1). Table 1 . A Idosteronism : Findings in Six Cases Low scrum potassium 6 Elevated serum sodium 6 ^^eakness 5 Polyuria 4 Headaches 2 Hypertension 6 Elevated aldosterone . 6 Range: 25 to 110pg./24 hr. Average; 41.6 fig. ?{ormsl values: 3 to 15 fig. Endocrinologic diffcreniiolion. Aldosterone cau«es retention of sodium and loss of potassium by Uie kidney. As a consequence, over- production of this hormone produces neuromuscular symptoms of 174 ADVANCES IN DIAGNOSTIC UEOLOCY muscular weaknc«s (in alt but one of the sU eases in^est^gated at llie Unj\ersity of California Mediciil Center),* uhich may be se* vere enough to cause paralysis, muscular tetany, and j»arcsthcsias; renal symptoms of increased %%ater intake and output (four of six cases), the latter occtirring espedally at night; and liypencnsi\e symptoms of severe headache (in two cases). TJic physical finding' are liy]»crtension (ranging in the cases iinestigaled from 210/1 10 to 160/100), positive Chvostek ami Trousseau’s sign*, cardiac en- largement, and, nnexjMjcledly, no edema. Laboralorj* finding', arc low levels of serum potassium (1.8 to 3.0 milliefpuvaleiits per liter in tlie present series), ele\aled senim sodium levels (141 to 153 milliequivalcnts per liter) and elevated carbon dioxide combining poncr (average 36.3 miUiefiuivaleiils per liter) and scrum pll. An increase in nldo'tcronc excretion is also evident. In cases of primarj* aldo«tcronism the average aldosterone level in the urine was 41.6 micrograms in a period of 24 Imur?, nilh a range of from 25 to 110, as compared to the normal levels nhich are 3 to 15 mirrugrams in a period of 21 hours. Tiic additional findings are albuminuria, alkaline or neutral urine, large urine volume of low specific gravity v>Iiich is unresponsive to decreased intake or PItrc*.«in, liigli ratio of urinary to scrum polas'lutn, »lecrca«ed rcn.il function (not infreipicntly ns'ocialcd nilh pyeloneplirilis), and electrocardiographic change> accompanying the hvpokalemia. Of course, the ti'iial |ulicnl nill not liavc all tliC'C symptoms and finding'. Hut a palieni ivitli liypcrlcnsinn and a low scrum potassium level is immedialcly sU'po<1, C'pecially if he has Iiead- nchc, neaknc'S, or polyuria. Disorders other than primal) iildo'teroni'm, such a» diarrheal disease and a poorly functioning ureterosignioido«lomy, may produce hypokalemia. Cu«hing*s syai- drome produces part of ihedescriltcd alterations in salt mpl.iboli«m, and renal Itihular acidosis produces lo^s of potassium. * Ilati on lUr,? by Dr. U«*r(l C. Itistirtt an.l t)r. rd'-r It FoniiaRL Diagnosis of Adrenal llyperfunction 175 A useful test for more certain diagnosis, utilized in five cases at tlje Universit)' of California Medical Center to differentiate aldosteronism from hypertension,^ Cushing’s syndrome, or renal tubular acidosis, is the administration of spironolactone to block the renal tubular effects of aldosterone. In all five cases spirono- lactone given for three days resulted in an increase in the serum potassium level of more llian 1.2 milliequivalents per liter, ^vith an associated increase in sodium excretion and a decrease in potassium Joss. Furthermore, all of these patients had an increased total plasma volume® \\ith a corresponding rise in total blood volume and a decreased hematocrit. Hjiicrtensive patients and liiose with Cushing’s syndrome did not have such a response to spironolactone and did not have increased plasma volumes. Sodium restriction^ may give helpful information in diagnosis, especially in tlie exclusion of “salt-losing nephritis” seen as renal tubular acidosis with chronic pyelonephritis, as well as in the exclusion of hyperparathyroidism, hypertensive nephropathy, liydroneplirosis, and llie secondary effects of urelero-lntestinal anastomosis, since by decreasing the amount of sodium presented to tlie tubule, potassium will be held back and urinary potassium will fall in hyperaldosleronism. Uadiograpliic dilTereniiaiion. Primary aldosteronism in four out of five cases is due to small adenomas,® which usually weigh from 1 to 3 grams. In tlie 6 cases Avhich we have investigated, the average weight was 4.6 grams, ranging from 1.5 to 8.4 grams, because they are small, their radiographic localization is diflicult, and transabdoniinal exploration is usually necessary. Moreover, 9 per cent of patients have bilateral adrenal cortical hj^ierplasia and 6 per cent have adrenal glands which appear normal.® In our experience, for example, a tumor weighing 8.4 grams in one patient showed only hordcrlinc enlargement by presacral gas in- sufllalion, whereas one wcigliing 4.5 grams in another patient was localized by gas study. It has been found that in about half of the cases tumors have been localized by presacral gas insufUa- 176 ADVANCES IN DIAGNOSTIC UROLOGY lion;* in the other case^ there have been either small tumors or hyperplasia, requiring hilaleral simultaneous surgical expo- sure. Treolnieni. Trcalnienl consist's of removal of the adenoma, of the rare carcinoma, or of mo«t of the hjqiertropliic adrenvvl glandular tissue if tumor is not present. The postoperative course is usually smooth; specific medicntion is not required, in contra*! to the postoperative procedure for adenoma producing Cushing’s syndrome. Potassium is retained and sodium U lost, water excre* tion falls to noirnal levels, the kidneys gradually regain their function, the hlood pressure returns to normal levels, and the other symptoms disappear. ADRENAl. MKDUl.LAItY 11 Y 1' Kit EU N CTl 0 N Plicocliromoe)tomas, like adrenal cortical tumors, must he identifictl l»ollt hormonally and anatomically l>efore surgical treat- nicnt is undertaken. EntJorrinolofiic Difffrrnllation Hormonal detection starts nilli suspicion of the presence of pheochromocyloma. P.iroxysmal attacks, hlcnlical to tho^e liiduwl hy injecitnl epinephrine and norepinephrine and pos^ihly confused with anxiety attacks, were seen in ten of the luelvc ea«es at this institution. Tlie typical symptoms arc headache, palpitation, vomiting, sweating, dyspivea, weakness pallor. vliErincss, snh- sternal or aUlominal pain, and nervousness. Persistent hyper* lev\s,vov\, Uowevet, doe*. vwA wv Uxvng a plveochxow Vumox to mind. A In-tor^* of paroxysms or evidence of increa'-ed inctahollc rate or of transient glycosuria may lie helpful. Small lumorp fonning small amounts of norepinephrine produce a clinical pic- ture similar to essential hypertension,” vvhereas tho-e tumor* forming larger amounts of norepinephrine may produce greater Diagnosis oj Adrenal Ilyperjunction 177 alterations in metabolism. Epinephrine-producing tumors, on the other hand, in addition to producing hypertension, cause more hypermetabolism, hyperglycemia, and tachycardia ijjan do norepi- nephrine-producing tumore; smaller amounts of epinephrine than of norepinephrine are required to produce these elTects. If pheochromocytoma is suspected, ll»e following testing pio- gram should be followed: 1. General provisions No sedation or narcotics are given for *18 hours before tests, and no antihypertensive drugs are administered for eight to ten days prior to letting. TUw&xme, tetracycUnt, and ate. v.Uhheld.-t 2. Histamine test {ij systolic blood pressure is less than ISO mm. Hg), using adrenolytic control a. Obtain basal blood pressure after ont-half hour of recumbency in a quiet room, 1). Perform cold pressor lest*< for control values by placing patient’s hand in ice water 1 minute, recording Wood pressure at 30 seconds and at CO seconds, then at every 2 minutes until level returns to basal value. If patient has a positive reaction to the cold pressor test, his response to histamine may he difficult to interpret. c. Give O.OS milligrams of histamine base in 0.5 cubic centimeters of normal saline solution intravenously "ith tuberculin syringe; im- mediately attadt a second syringe containing 5 milligrams of Regi- tine fphentolamine). d. Determine blood pressure every 30 seconds. Pressure wilt fall at first (this drop in blood pressure triggers the tumor response) , and then, if the test is positive, it will rise to hypertensive levels. e. Give S milligrams of Regiline 2 minutes later. Blood pressure will return from the stimulated hypertensive level to normal in 1 minute (it may rise again if the tumor is large). Lack of response to the adrenolytic agent casts doubt on the diagnosis of pheocliromocy- toma. 3. Test for catecholamines in urine Wliile patient is hypertensive (use histamine for stimulation if neces- sary), collect 2Whour urine specimen in bottle containing 10 cubic centimeters of strong acid. Normal excretion of catecholamines is 20 to 55 micrograms per 2 1 hours; with pheochromocytoma at least 100 and 178 ADVANCES IN DIACXOSTIC UROLOCT usually more Uian 300 micrograms are excreterl. If only epineplirine is found, ihe tumor is most likely estra-adrenaL 4. Other tests a. Dibenamine and benzodioxane are otber adrenolytic agents, but both bare sympatbolylic effects, especialir dibenamine, vrhtcb in addition has a rather prolonged effect. Regitine therefore is the preferred drug. b. Pressor amines in serum may Le determined in the absence of jaundice, azotemia, or lymphoma. Blood is spun dovm and frozen for shipment to the laboratory. Normal leieU average 2.S micro- grams per liter; tumors raise the«e letel* to from 0.0 to 360 micro- grams.si c. (3*melhorr. 4-!ivdrocMnandeIic acid), a urinary metabolite of epinephrine and norepinephrine, has a normal range of O.S to 2.0 znlcrograms pec milligram of creatinine. The patient uith pheo- chroroocctotna excretes 6 to 40 micrograms. TIu* test is u«eful as a screening deitce. and it is more reliable than actual measure' ment of the catecholamines. In ihe series of 12 ease* of pfaeocbromocvtoTDa studied at the Unirersily of California Medical Center,* 5 li.id histamine tests nliich established the diagnosis. Ten patients had posithe Regitine tests (one bad a positi^ e bistaroine test but a negalu e Regitine test ) . Urinary catecholamines ivere measured in 9 patient*, rising as higli as 2000 milligrams per liter and measured as norepinepbn'iie. Patients with sustained hypertension had consistently high senmi and \ery high urine values of norepinephrine. Those A\illi par- oxysms, as would be expected, had le>s consistent xaluc*. In fact. 2 of the patients had nonnal Jerels of urinary catecholamine,*. BadiogropMc Di0erenriarion The sites of pheochromocyiomas lia\e been reported as follows; right adrenal, 41 per cent; left adrenal, 35 per cent; extra-adrenal, 14 per cent; and bilateral, 10 per cent.** In out series 7 of 12 • Tea Aew 12 h»ve btta reported ia peater tJeuU by IflU lod Smitb.** Diagnosis of Adrenal II yperf unction 179 ^vere in the right adrenal and 5 were in tlie left adrenal; none was extra-adrenaU Most of lliose placed extra-adrenally have been found in t)je paravertebral space;*® leas than 5 per cent n'ere prcaortic, in (he organs of Zuckerkandl, or in some other area usually not visible by presacral gas insufllation. Therefore localiza* tion by roentgenography is considered possible in a high proportion of cases. The size of a pheochromocyloma is such that preoperative localization is iisually possible. Tlie smallest tumor removed at our institution weighed 10.1 grams and the largest 490 grams, average weight being 120 grams. Bilateral instances (especially prevalent in familial cases) may he overlooked by giving loo much attention to the side witlt tlie most obvious tumor; of course, because removal of the larger tumor does not cure tlie disease, a second operation must he per- formed in such cases. Intravenous urograms were done in 11 of the 12 cases in the series. In 3 cases the side of involvement was suggested by dis- placement of die upper pole of die kidney downward and out- ward, In 8 cases the urograms uerc interpreted as showing no disease, and plain tomograms did not add furtlier information. Presacral gas insufllalion was performed in 10 cases and demon- strated an adrenal mass in all hut one case. In this case, previously reported by Hill and Smith,*® urograms and two presacral oxygen studies did not reveal the site of the tumor. An aortogram, how- ever, showed a vascular mass above the right kidney 2 centimeters in diameter; this mass was subsequently removed. If tlie simpler methods of localization fail, aortography is especially helpful in visualizing the highly vascular pheochromocjr'toma (see Chap. 1). Surgical Management We are operating for pbeochTomocyloma on relatively young patients (the average age in this series was 36 years, liie range from 17 to 59 years). 180 ADVANCES IN DIAGNOSTIC UROLOGY Premedication is important. One of tiie patients was found to have suffered a stroke, presumably from preoperative hyperten- sion, sometime before going on the operating table, so that opera- tion had to be deferred until she was stabilized. Rapid moniloiing of the blood pressure »s also necessarj*, but arterial catheterization for this purpose is probably tunvise because a continuous record- ing is not e«senlial and may produce serious complications.’® Control of the blood pressure during introduction of anesthesia is accomplished by providing an adetjuate venous cannula con- nected tlirough proper stopcocks to three bottles, one with dilute Hegitine (5 milligrams per 100 cubic centimeters of 5 per cent dextrose in water), the second with Levophed (L-norepineplirine), and the third with 5 per cent dextrose in water. Thus the endo- crinologist, anesthetist, or surgeon may correct both hypertension and hypotension. Special attention must be paid to Regitlne ad- ministration nhen tbe tumor is exposed and manipulated, and to Leiopbed therapy at the time the venous outHow is clamped. Since the circulating blood volume is decreased by the pre-existing hyper- adrenalism, it will no longer fill the vascular bed when the tumor is removed^ consequently transfusion of nhole blood is often needed even though operative blood loss does not demand it. Levophed is used to supplement the transfusions and, if necessaiy, may be continued for several days. Replacement therapy with adrenal steroids {«• not needed unless bilateral adrenalectomy is performed for rare bilateral tumors. Failure of the blood pressure to return to normal after operation suggests the presence of another pheochrome tumor. Operative exposvire is Iresl achieved by tiie flank approach, elfiier suLdiapliragmalically liy excision ol the eleventh rih or through tbe cbest by an incision between tlie ninth and tentb ribs. Perhaps the latter approach should be reserved for large tumors, since it opens greater possibilities for complications. For two rea«on« the surgeon is at serious disadvantage if he cannot localize the tumor before operation. First, if the tumor is Diagnosis of Adrenal Uyperfunction 181 situated suprarenally, it lies in an area of the body very difiicult to expose adequately from the front. Second, if the tumor is extra- adrenal, on extensive search of the entire syrapatlietic chain from diaphragm to aortic bifurcation may be required. For these reasons we utilize presacral gas insuillalion in all cases. REFERENCES 1. Dartter, F. C., and BigJieri, E. G. Primary aldosteronism; Clinical staff conference at llie National Institutes of Health. Ann. Int. Med. 48:647, 1958. 2. Bergenstal, D. M., Lipsett, M. B., Moy, R. H-, and Herr, U. R^res- sioR of adrenal cancer and suppression of adrenal function in man by op'BDD. Tr. A. Am. Physicians 72:341, 1959. 3. Biglleri, £. G., and Forsham, P. H. Studies on the expanded extracel- lular fluid and the responses to various slimuii in primary aldostero- nism. Am. J. Med. 30:564, 1961. 4. Diglieri, E. G., Slaton, P. E., Jr., and Forsham, P. H. Useful param- eters in the diagnosis of primary aldosteronism. J.AM.A. 178:19, 1961. 5. Conn, J. W. Evolution of primary hyperaldosteronism as a highly specific entity. J.Ajf.A. 172;1C50, 1960. 6. Conn, J. W. Primary aldosteronism. /. ini'. «£* Ch'n. /1/ed. 45:6, 1955. 7. Cope, C. L., and Harrison, R. J. Effect of 9*o-(luorohydrocortisone on adrenal liyperfunction in Cushing's syndrome. Sril. M. J. 2:457, 1955. 8. Delorw*, P., awd J. Piiwaiv aldostMOWMo.*. A. review of tUe medical literature from 1955 to June 1958. Canad, M.A.J. 8:89J, 1959. 9. DiRaimontlo, V., Hane, S., and Forsham, P. H. A criterion for the choice of bilateral total vs. subtotal adrenalectomy in Cushing's syn- drome. (Abstract) Clin, Res. Proc, Srf»9, 1957. 10. Gold, E. M., Kent, J. R., and Forsham, P. II. Clinical use of a new diagnostic agent, Methopyrapone (SU-1883), in pituitary and adre- nocortical disorders. Ann. Int. Aled. 5 4:175, 1961. 182 ADVANCES IN DIAGNOSTIC UROLOGY 11. Goldenberg, M., Serlin, I., Edwards, T., and Rapport, M. M. Chemi- cal screening rnethods for the diagnosis ol pheochromoc}toma: 1. Norepinephrine and epinephrine in human urine. Am. J. Med. 16:310,1934. 12. GraKam,J.B. Pheochromocjloma and hypertension. /niernal. Surg. 92:105, 1951. 13. Hill, F. deM., and Smith, D. R. Pheochromocytoma: A report of 12 cases, California Med, 92:125, 1960. 14. Hines, E. A., Jr., and Brown, G- E. A standard test for measuring the variability of blood pressure: Its signiheance as an index of the prehypertensive stale. Ann. Int. Med. 7:209, 1933. 15. Hillman, F., Jr., Steinbacli, H. L., and Forshain, P. H. Preoperative differefttialton between hyperplasia and tumor in Cushing’s syndrome. Tr. Am. A. GenitO'Urin. Surg. 48:97, 1956. 16. Holmes, R. 0., Moon, H. D., and Rinehart, J. F. A morphologic stud}' of the adrenal glands with correlations of body size and heart size. Am. /. Path. 27:724, 1931. 17. Landes, R. R., and Ransom, C. L. Technique for the use of carbon dioxide in presacral retroperitoneal pneumography. Surg. Cynec. & Obit. 195:268, 1957. 18. Liddle, G. W., Island, D., Lance, E. M., and Harris, A. P. Altera- tions in adreual steroid patterns in man resulting from treatment with a clinical inhibitor of ll-/7-hydroxyfalIon. J. Clin. Endocrinol, 18:906, 1958. 19. Poisnick, J., and DiRaimondo, V. Adrenal function in obese women. (Abstract) /. Clin. Endocrinol. 16;957, 1936. 20. Ransom, C. L., Landes, R. R., and McLelland, B. Air embolism following retroperitoneal pneumography: A nation-wide survey. /. Grot. 76-.6a, 1956. 21. Roth, C. M., Flock, E. V., Bollman, J. L., and Kvale, W. F. Evalua- tion of (he pharmacologic and chemical tests as an aid to diagnosis of pheochromocytoma. Angiology 10:426, 1959. 22. Sofler.L. 3., Dorfman,R.l„ andGahrilove, J. L. The human adrenal gland. Philadelphia; Lea 8. Febiger, 1961. Diagnosis of Adrenal Uyperfunction 183 23. Steinbach, H. L., and Smith, D. R. Extraperitoneal pneumography in diagnosis of retroperitoneal tumots. AM.A. Arch. Surg. 70:161, 1955. 24. Steinbach, H. L., Hinnian, F., Jr., and Foraham, P. H. The diagnosis of adrenal neoplasms by contrast media. Radiology 09:664, 1957. THE RADIOISOTOPE RENOGRAMs 9. A KIDNEY FUNCTION TEST The radioisotope method of determining individual kidney func- tion •^\a8 first developed and almost immediately put into clinical use in 1955 at the University of California Medical Center in Los Angeles. The first experiments xvtUi radioiodmated Urokon (Urokon-F^^) and Dlodrasl-I*®^ produced similar characteristic renograms in rahbits and dogs, hut only Diodrast was appllcnhle in the human lieiiig. Unfortunately Diodrast is also excreted in small part by llie liver, and because of its rapid transit time through renal tissue, it is not an ideal lest agent for kidney studies. Since that time, ten test agents with three radioisotopes liave been studied clinically, culminating in the use since early 1960 of Hippuran-P^'^ and even more recently of Hippuran-P"®. The conventional term in the United States for this test is the radioisotope renogram. Researchers in some European countries prefer the term radtoijo/ope nepArogr«m> which, allhougli more linguistically precise, is also used to describe the roentgen picture of the kidney when h stands out sharply in relief from other tissues. Renogram therefore seems more suitable, since it has no other ii^e in medical language. 184 The Radioisotope Renogram: A Kidney Function Test 185 TECHNIQUE AND EQUIPMENT Tlie principle of the radioisotope renogram is radiation pro- jection analysis. A minute amount of test agent, labeled with a proportionately small amount of radioisotope tracer, is injected intravenously. Because the material is selectively excreted hy the kidney, continuous radiodeteclion over the organ will show a characteristic rise and fall of the level of radioactivity as the material is secreted and excreted hy the renal tulmles. By using two radiation detection and recording units, both kidneys can be tested individually and simultaneously. A third unit over the upper chest will reveal tlie blood clearance rale. Optimal equipment, therefore, consists of tliree highly sensitive scintillation counters wliich are efRcienl in tlie detection of the photons of or T®*, and three medical rate meters connected to three strip chart recorders. The patient typically is seated in an upright, comfortable posh tion (Fig. 1), and both kidneys are located by an upriglit roent- genogram. To achieve an accurate result, tlie precise location of the kidneys is paramount in the performance of the test. Guessing at the anatomic position of the kidneys or using a scanning tech- nique to find the kidneys has not proved as accurate as use of roentgenography. Infants or seriously ill patients may he tested in the prone position or on their sides. Although these positions are satisfactory from the standpoint of achieving results, they are not as convenient nor as precise as the preferred position. The twelfth ribs, vertebral coliimu, and crests of tlie iliac bones serve as landmarks in positioning the counters at right angles to the posterior aspect of each kidney. The patient need not disrobe, although baring the kidney area is desirable. The dose of test agent is computed according to body weight and is rapidly injected intravenously as a bolus. 186 ADVANCES IN DIAGNOSTIC UROLOGY Figure 1. The slandacd unit coa^isCs of tu’o sctutillation counters directed at right angles to tlie posterior aspect of each kidoey, os shoivn. A third counter (not shoivn) is placed oter the chest to measure hlood clearance. Afatched rate meters and recorders complete the renography equipment. W}ien is used, a scinliUalion couiilei with a 1-inch crystal, collimated with l-inch thick lead, is most suitable. Because of their lieavy weight, large, sturdy stands are necessary to hold the counters. With the use of I*®® and its soft gamma and roentgen rays, light scintillation counters utilizing crystals 2 millimeters thick and transistorized scintillation counters with thin brass col- limators are ideally suited for its detection. Light, less bulky stands are permitted with these small, light scintillation counters. The rale meters may be of standard tyj)e or transistorized; tJie latter are lighter and less bulk)'. Finally, the recorders may be of the Esterline-Angus, Texas, or Kustrak type. The latter, again, are quite small, and it is possible therefore to improvise a unit weighing approximately 50 pounds which could be transported easily. Although linear rate meters are more popular and less expensive, logarillimic tale meters may be utilized with about The Radioisotope Renogram: A Kidney Function Test lft7 equal results. Use of the logarithmic rate meter always guarantees a tracing ivilhin the range of the strip chart. INTEKPUCTATION The normal renogram characteristically lias three segments (Fig. 2). The initial spike, 20 to 25 seconds in duration, is rouglily proportional to the vascular capacity of the kidney. Tlie second rise of the tracing is an index of the tubular function, and the terminal fall in the tracing indicates clearance of the radioactive urine. A small portion of the radioactivity emanating from the kidney region is due to radioactivity of adjacent tissue. IXTien the kidney is absent there is a short initial spike followed by a menta: (a) Uie initial spike corresponding to renal vascular capacity, (t>) the secondary rise indicating renal functional ability, and (c) the terminal descent reflecting ability of the kidney to evacuate urine. Tlie blood clearance tracing (dotted line) shows a sharp drop during segment b of the renogram. 188 ADVANCES IN DIAGNOSTIC UROLOGY gradual fall in the tracing which corresponds to the blood clear- ance tracing. Tlie latter tracing is valuable in showing total kidney function, which is indicated by the percentage fall in the tracing from the fourth to the sixteenth minute when measured over the upper chest (Fig. 3). Some investigators have modified the renogram by placing an extra counter over the bladder region, a metbod wbicb they think would correspond in reverse to the blood clearance method. In our opinion this method is not as accurate and is subject to too many variables that have nothing to do with kidney function. Another modification of the renogram has been the ratio-meter tracing, which involves subtracting radioactivity of the recessive kidney from that of the dominant one. Other researchers believe that individual diffeiences in kidney function can be detected in TRAY ACTJVtTY CTS/SEC Figure 3. This renogram of unilateral renal disease shoi^s a marked reduction in both vascular capacity and functional ability of the right kidney compared with the normal left. The blood clearance (dotted tracing) shows a normal descent between the fourth and sixteenth minutes (X to A ). Its value is computed by dividing Af® — A*^ into A’-t — A^*. The Radioisolope Renogram: A Kidney Function Test 189 a more sensitive fashion hy giving a carrier dose of the test agent prior to the renogram test in order lo saturate or block the tubule cells. Then, by waiting a period of lime for partial saturation to occur, the kidney with the belter function will be differentiated more easily. This technique remains to be proved and accepted in place of the standard renogram technique. The most sensitive portion of the renogram tracing would appear to he the third segment, or the evacuation phase. Any obstructive uropatby will cause this portion of the tracing to drop less ex- ponentially or fail to fall at all. Another condition that affects the terminal tracing is decreased renal function from ischemia or shock. The second most sensjlive portion of the tracing is the second segment, or the functional portion of the renogram. The preparation of the patient required for other tests is not necessary for routine renography. However, t)ie rejjogram tracing may be altered somewhat by the slate of hydration. In the over- hydrated person the test agent usually passes through the kidney more rapidly, making the secondary segment rise faster and caus- ing the test to be consummated in a shorter time. Dehydration will produce a longer second segment rising to a lesser height and will also tend to prolong tlie excretory (third) segment. DlAG^OSTIC VALUE Various degrees of renal dysfunction may he represented hy a decrease ox prolongation of the second segment. However, none of these findings is diagnostic for a specific disease entity; they only give qualitative information regarding tlie function, blood supply, and drainage of the kidney. Tlierefore the radioisotope renogram does not replace intravenous pyelography or aortog- raphy, or for precise quantitative information, the individual standard renal function tests. It is supplementary', being most use- ful as a quick screening test of kidney function among large 190 A.BVANCES IN DIAGNOSTIC UROLOGY numbers of individuals. The renogram is also used to screen hypertensive patients in order to find those with unilateral or bilateral renal disease (see Chap. 5, Fig. 1), to determine the status of the kidneys prior to operation, to show llie results of operation, and to follow patients with medical or surgical disease by serial renography. The use of renography in acute renal failure is valuable within the first 48 hours in that it can differen- tiate bilateral, total ureteral obstruction from acute renal failure and severe dehydration; after 48 hours the tracings tend to become more similar. However, if xenography is used early in anuria, the tracing of bilateral ureteral obstruction will show good functional segments with continued rise in the third phase. Those tracings of acute renal failure will show absent or only slight functional seg- ments without the rise in the tracing nnd with a very gradual drop in the tlurd phase. The advantages of the renogram are its ease of performance, the lack of hazard, trauma, or pain to the patient, the tepidity with which it is performed, and the immediate availability of results for interpretation. Although the equipment is expensive initially, there is now hope that through the use of the cost of recorders and rate meters may l»c decreased; the cost of scintil- lation prolies, hoivever, will piohaldy remain about the same. Tlie co&t of the stand needed for the I’"® renogram should also he reduced sharply. The lest agents for renography are not ex- pensive per dose per patient, and the shipping charges for I*"® are less than for because its photons are absorbed readily by tin and do not require the lead jacket used with Tlie re«uhs of renography have correlated well with other clinical tests such as the clearance techniques and dye tests. These latter tests have themselves been 85 to 90 per cent accurate as compared with the total kidney function picture, while the reno- gram has been found to Ije 85 per cent correct. Tlie tests are not mutually exclusive, but are complementary’ in determining uni- lateral renal disease and sliowing the effect of renal-arterial Vie Radioisotope Renogram: A Kidney Function Test 191 esions. Il should be kept in mind that the renogram is a quali- alive test. tlEFERENCE 1. Winter, C. C. Radioisotope Renography. Baltimore: Williams & Wilkins, 1963. 10 . RENAL PHOTOSCANNING IN HROLOGIC DISEASE ROBERT 0. PEAR MAN* Radioisotope pliotoscannmg of the kidneys ^vith a radioactive tracer is a technique for graphically recording a clearly delineated spatial image of the kidneys. This procedure records the sizct shape, composition, and function of renal parenchyma. Areas of greater or lesser renal function are visualized as darker or lighter areas on the renal photoscan. The procedure that permits the visualization of an internal organ hy determining the spatial distrihulion of a gamma radiation* emitting isotope svitUiu it has made rapid progress since 1950. At that time Casseii and associates’ employed die newly developed scintillation counter and a mechanical printing device to determine the distribution of radioactive iodine in the thyroid gland. Kuhl and associates^ improved the IcchiiH|ue liy replacing the mechanical printer with a llashiiig light that activated the photographic emul- sion on Toenlgenographic film. Bender* was instrumental in the development of this procedure for clinical use. Radioactive contrast media such as raclioiodinated labeled) Diodrast, Miofcon, Urokon, and Hippuran have been Avidely used for renal function studies® excellent • The ttnilior vii'hes to scknowIeJee ibe as'iMance of Dr. William Blahil, Chief of the Radioisotope DuUion, Vetetans AdnutiatTation Center, Los Angeles, in thU stodj'. 192 Renal Photoscanning in Urolo^c Disease 193 results. However, lliese substances appear to be unsatisfactory for pholoscanning because of their rapid excietion by the kidneys without significant retention in the renal parenchyma. Borgligraef and associates® in 1956 reported that mercur)- 203 (Hg®®®) and clilormerodrin (Neoliydrin) are rapidly taken up by the renal cortex, temporally fixed within the tubular cells, and excreted in the urine. Delay in the onset of diuresis following the intravenous administration is related to the time required, generally 50 to 80 minutes, to accumulate a critical concentration of the drug within the tubular cells of the kidney. Two hours after an intravenous dose of 100 to 150 microcuries of Hg®'’h labeled cldormerodrln, the pholoscan study is performed. With the patient in tlie prone position, the scanning is carried out with a scintillation photoscanner.* Because of higli plasma binding, most of the mercury excreted in the urine is eliminated by tubular secretion. By a series of ingenious experiments in which they injected 1 milligram per kilogram of Hg®®®-labeled chlormerodrln into dogs, the.^e researchers showed that llie plasma concentration of this material regresses as a multiple exponential function of lime. Three exponentials were identified with lioIf*limes of 0.5 to 1,5, 6 to 9, and 50 to 80 minutes respectively. They found that the first of these exponentials agreed reasonably well wdih the initial regiession of the plasma concentration of Evans Blue wlien the dye and diuretic were administered simultaneously, i.e., tlie physical process of mixing within the circulating volume of plasma. It was shown that the second exponential represented an average of the rates of transfer of mercurj’ from the plasma to a variety of tissues and organs, perfused at varying rates and exhibiting diiTerenl affinities for the diuretic. The administration of BAL (Britisli Anti-lewisite) with the clilormerodrin greatly in- creased the difFusibility of the mercut)’ and its uptake hy all tissues Ollier than the kidney. Tlie third exponential was dominated • Picker MagnMcanner. 19t ADVANCES IN DIAGNOSTIC UHOLOCY by renal excrelion; bilateral nephrectomy demonstrated tin’s fact and revealed that extrarenal clearance takes place to an ap- preciable degree through gastrointestinal secretion. McAfee and T^^agner® demonstrated that tlie diuretic clilor- merodrin labeled with radioactive mercury was retained in the renal parenchyma long enough to permit renal pholoscanning. They observed that the effective half-life of Hg'°^ within the body was quite short, an average of 3 hours, so that the radiation dose to the kidney %vas minimal, less than 0,5 rad, despite the 45-day physical half-life of Furthermore, the nucleide Hg®®’ had a single, ratlier weak gamma emission (280 Kev.) that facilitated good resolution when a multiport focusing collimator and gamma spectrometer were used. renal function is very poor, the labeled diuretic tends to concentrate in the liver, from wliich it is slowly excreted. These pharmacologic and physical character- istics make it possible to obtain a clearly delineated spatial image of the human kidneys by means of radioisotope photoscanning. Herring® slated that the interpretation of any pliotoscan involves two distinct problems. First, it must be determined how well the scan data recording system accurately portrays the input data, whicli are strictly statistical, and to what extent these data record every information-carrying photon with true fidelity, free from distortions and artifacts. A scintillation photoscunner, utilizing a 19-hole collimator, a 3-incli by 2-inch sodium iodide crystal, a pulse height anal)’zer, o pulsed light photorecording system, a dot recording mechanism for observing the progress of die pro- cedure, ami an integrated drive mechanism, answers these criteria. The second, much more formidable, problem is to establish uhich scan patterns constitute normal or aVmormal distribution of radio- isotopes so that the presence or absence of disease may he de- termined. Tlie diagnostic armamentarium of the urologist lias approaclied perfection to a degree found in few other specialties. However, the variant renal arterial blood supply and the “spotty” nature 198 ADVANCES IN DIAGNOSTIC UROLOGY 6. Tlie plioloscan will record an image of tlie kidney wlien llie creatinine lerel is elevated and poor renal function precludes satisfactory visual- ization on an etcretory urogram (Figs. 5 and 6). 7. The renal pholoscaii helps decide whether or not a visualized cal)x on the excretory urogram represents function of lliat segment of the kidney or mere retrograde itlUng from the renal pelvis. 8. Certain ambiguous findings on the renal arteriogram may be clarified by the renal pholoscan (Fig. 7). 9. Segmental or polar lesions of the kidney can he demonstrated (Fig 8 ). 10. The procedure is painless, harmless, and easy to perform. I Figure S. Atrophic left pelvic kidney. Renal Phaioscanning in Viotogic Disease 199 figure 6. Bilateral contracted ktdnep,* no function on intravenous p}c]og'ram; creatinine 4.5 milligrams per cent. Tlic renal pholoscan has proved valuable in localizing renal cysh and tumors, and in delineating Itorseshoe kidneys, duplex kidneys, polycystic kidneys, ectopic kidneys, and atrophic kidneys. The procedure also appears to be of diagnostic value in patients Figure 7. Multiple infarcts on left kidney. 200 ADVANCES IN DIAGNOSTIC UKOLOCY figure S. Ischemic lower pole right kidne) in patient with renovascular h)perlen8ion. with suspected renovascular hyj)erlension, c^pecially Uiose with segmental ischemic renal lesions. The urologist svilh imagitialton and an interest in the fields of nuclear physics, electronics, and radiopharniacology will be- come intrigued with tlie possibility of enhancing liis diagnostic acumen by employing the painless and harmless procedure of radioisotope renal photoscanning. In this virgin field, where one often learns to write before lie learns to read, it is easy to become discouraged with the results of trial and error and with the limitations of the procedure. Attention to detail and increased experience in interpreting the renal pliotoscan will probably lessen the percentage of interpretive error and iuetejite the value of this complementary diagnostic screening procedure in renal disease. No definite conclusions can be drawn from the early observa- tions, but evidence to dale indicates that this urologic technique promises to be a valuable tool for tlic detection and difTcrentialion of certain lesions of the renal parencliyma which are often diflicult Renal Photoscanning in Urologtc Disease 201 to detect accurately by other currently employed urologic pro- cedures. REFERENCES 1. Bender, M. A. Pliotoscanning detection of radioactive tracers in vivo. Science 125:443, 1957. 2. Borgligraef, R. R. M., Kessler, K. H., and Pitts, R. F. Plasma regres- sion, distribution and excretion of radiomercury in relation to diure- sis following tbe intravenous administration of Hg 203 labeled cblormerodrin to the dog. /. Clin. Invest. 35:1055, 1936. 3. Cassen, D., Curtis, L, and Reed, C. Sensitive directional gamma- ray detector. Nucleonics 6:7C1. 19.50. 4. Haynie, T. P., Stewart, B. H., Nofal, M. M.. Carr, E. A., Jr., and Beterwaltes, W. H. Renal vascular disease and tumors by photo- scanning. J.AM.A. 179:137, 1962. 5. Herring, C. E. Universal photorecording system for radioisotope area scanners. J. Nucl. Med. 1 :83, 1960. 6. Kaufman, J. J., Schanebe, A., and Maxwell, M. Intravenous uro- gram in renovascular hypertension: Methods of enhancing its diag- nostic value. ]. Ural. 89:498, 1963. 7. Kuhl, B. E., Chamberlain, R. H., Hale, J., and Corson, R. 0. A high- contrast photographic recorder for scintillation counter scanning. Radiology 66:730, 1956. 8. McAfee, J, G., and Wagner, )!. N., Jr. Visualization of renal paren- chyma by scintiscanning with Ifg 203 Neohydrin. Radiology <5:829, 1960. 9. Nordyhe, R. A., Tubis, M., and Blalid, W. Tlie use of radiniodinated Hippuran for individual kidney function test. /. Lab. & Clin. Med. 56:138, 1960. 10. Sklaroft, D. M., Berk, N., and Kravitz, C. The renal scintigram in urologic v\orfc-up. J.A.M.A. 178:418, 1961. 202 ADVANCES IN DIAGNOSTIC UROLOGY 11. Taplin, G. V. Radioisofope ren<^am: External lest for indhidual function and ujiper urinary tract patency. /. Lab. & Clin. Med. 4S: 886. 1956. 12. Wagner, IT. N., Jr., McAfee, J. G., and Mozley, J. M. Medical radio- isotope scanning. J,A.M.A. 174:102, 1900. 13. Winter, C. C. Unilateral renal disease and hypertension: Use of radioactive Diodrast tenogram as screening test. /. Urol. 78:107, 1957. Id. Winter, C. C. Further experiences with radioisotope renogram. Am. J. Roentgenol. 82:062. 1959. 15. Winter, C. C., and Taplin, C. V. Clinical comparison and anaijsis of radioacthe Dioc1ra*t, flypaque, Miokon, and Urokon renogroms as tests of kidney function. /. Urol. 79:573, 1958. IX. NEUUOLOGIC UltOLOGY ERNEST BORS AND RODERICK D. TURNER Today patients ,vith neutogenic disorders o£ caused either by trauma or disease of the J '7;’ look fortvard to better health and s^.al hcfore. In tl.e last 20 years many advances tlio management of neutogenic bladder y» unc , y cause since World War II interest has been ™ ^ and on the survival of its paraplegic vtct.ms In - recognized that teamwork is a necessity .n the f vitl. spinal cord trauma and that the team must con of rep sentatives of almost a dozen medieosurgteal specialties. It was also a, tl.at time .ha, the exposed to team conferences and could fami la ,„r borderline problems in :Lto::^t hU colleagues. Thus U ''as inevita nnt onlv worked confronted with a primarily neurolog.c cond, ton. in close association with the neurologist and hut also was wX^^icr.™^ anatomy and neurophysiolog) as • ii,c. fipM of nostic Lhods. From these effoits and experiene. the fieU o^ neurologic urology eventually emerge ’ narticular in- specialties, such as ophlhalmoloCT J organ— terest in neurologic disorders limited to a speci in the case of urology, tlie urinarj' bha er. 203 20 1 ADVANCES IN DIAGNOSTIC UROLOGY In the quest for diagnoslic analysis and rational therapy, it was also inevitable that relined, systematic methods of examination came to be devised in close conjunction with the allied fields of neurology, neuiophysiology, neurosurgery, and psychiatry. As in ophthalmology and otiatrj', methods of examination have evolved in urology that re(|uire special training to perform and evaluate and that cannot be done by anyone other than the urologist, upon whom other specialists rely for answers, Tlic urologist in turn seeks assistance from the neurologist, neurosurgeon, or psychiatrist nhen the situation demands consultation. Neurologic urology poses interdisciplinary' problems in diagnosis and therapy. These problems are not limited to the triad of neurology, neuro- surgery, arid psychiatry, but may include internal medicine, physical medicine and rehabilitation, plastic surgery, ortliopcdic surgery, orthotics, social work, and the unlimited field of tlie general practitioner, uho, as friend and father confessor of the patient and his family, will supply some of tlie most revealing information. Tlie importance of a good history is well known to all physicians, and it Is especially important in the field of neurologic urolog)*. Obtaining a good history is a painstaking labor of detection, but the reward is high and the time well spent. The process of examina- tion, loo, requires more lime than is usually necessary in general urology. In order to facilitate a systematic review of history and examina- tion in neurologic urology, we hav’e developed an outline which is based upon the experience of many years and is in use at the University of California Medical Center in Los Angeles. This outline is reproduced in detail in Appendix I. Once the data are collected and lecorded, the outline becomes the basis for further management, including repeated visits or consultations as they are necessitated by the changing status of the neurologic condition, llie first page of the outline serves as an ablireviated Neurologic Urology 205 record of tlie Idglilights of llie respective case; the remaining pages constitute a step-by-step guide for details of history and examina- tion. Neurologic disorders of the urmar)' tract are classified into upper and lower motor neuron lesions. Since ^^e are confronted by a basically neurologic problem, it behooves us to apply to it a neurologically accepted and concise terminology. We have found tliis outline helpful in organizing our thinking toward the diagnosis, completing our study in an orderly and systematic manner, facilitating follow-up studies, and achieving coordination with the consulting specialists. Tlie following discussion is organized according to the format of the questionnaire in Appendix I. THE HISTORY The history should be taken in detail. Tins is particularly im- portant in cases of nontraumalic neurologic bladder dysfunction, witli a slow insidious onset and occasionally traceable to child- hood or adolescence. Changes in micturiiion of any type leading to such disturbances during these periods of life may give a lead to the type of neurologic disorder. The inenarche may suggest an endocrine di«order. The urologist may be the first to detect a long- standing iiistory of diabetes by finding the clinical signs and symptoms of a neurogenic bladder. It would be fallacious to treat such a patient hy urologic methods when correction of the diabetes would in some cases resolve the neurologic problem. The bisJojy of bowoj rJoseJy jwjjaJJids or may roDecl the neurologic condition of the urinary bladder. Since both the rectosigmoid and the urinary Madder willi the e.vtenial urinary spiiincter arc supplied hy sacral segments of the conus, a hi&lory of constipation might be the only early complaint. Patients who move their bowels only every two or ibree days and nnIio have 206 ADVANCES IN DIAGNOSTIC UEOLOCY voiding problems sliould bave a complete neurologic evaluation. Artificial initiation by catliartics, supposilorie«, enemas, or rectal digital stimulation is abnormal, A disease determined from the history, such ns syphilis, par- kinsonism, combined degeneration, multiple sclerosis, poliomye- litis, or encephalitis, may he the cause of the patient's present problem. Habits sucli as nicotine, alcohol, and drugs affect the central nervous system and may influence bowel and urinary function. Accidents should be recorded because of their potential neurologic sequelae. Tlie type of accident, the position of the patient and bis state of consciousness at the lime of the accident, and the ana- tomic part of tlie body that was Injured should be listed. Operations, especially those on the bony spine and central nervous system, should be recorded. Radical pelvic procedures of the lectum or uterus deserve consideration because of possible interference with mlcturitional pathways. PltESCNT COMPLAINTS— VOIDING HISTORY The onset of tlie urologic problem, either from an illness or accident, will establish a date on which the first micturitional changes occurred. Most patients with neurogenic bladders have a mental picture of the previously normal act of micturition, unless the condition was congenital or developed in the first years of life. If the patient has a feeling of relief following micturition, the lesion cannot be complete. Tims a simple question will delect the exteul of a neutologic leatou in Uwi absence of ubstuictive utopaUvy . Tlie analysis of several sensations connected with voiding is informative. The absence of the desire to void indicates inter- ference with the afferent pathways from the bladder to the cerehral cortex. In tlie presence of motor dysfunction without obstructive uropathy, the normal desire to void indicates a lesion of efferent l\’eurologic Urology 207 bladder pathways. The pathways of the “desire to void” have been studied and are known.® The sensation of “micturition is imminent” indicates that the proprioception (position sense) of the striated pelvic floor muscles is intact. This position sense is conducted by the pudendal nerves to the spinal cord and the brain, and interference with these path- ways abolishes the sensation. If the sensation of “micturition is in progress” is present, tem- perature, pain, and proprioceptive pathways are intact from the entire urethra to the central nervous system (because of the short- ness of the female urethra, tins may not he valid in women). AI)sencc of this sensation indicates interference with the three pathways in either the pudendal nerves, tiie spinal cord, or the lirain. The information gained from allied sensations such as bladder distention or fullness and suprapubic, abdominal, or pbattlom fullness may .suggest tlie sensory level of a lesion. Vague sejisa- tion of bladder distention indicates a lesion at or below the twelfth thoracic segment of the cord. Suprapubic fullness may ])e ex< perienced if the lesioti is at or below the tenth thoracic segment. If there is only abdominal and not suprapubic fullness, tiie lesion is probably between tlie sixth and tenth thoracic segments. If the lesion is above tlje sixth thoracic segment, the patient experiences autonomic dysrcflexi.i manifested by paroxysmal hypertension, bradycardia, headache, sweating, goose pimples, chills, clogging of the nasal airways, and flushing of the face and neck. The cliaracter of the initiation of micturition (normal, precipi- tate, reflex, strain. Crude) can be hifonnative. Precipitate micturi- tion, a sudden uncontrollable urge to void, indicates an incomplete tipper motor neuron lesion. Reflex micluriliou, spontaneous void- ing unbeknown to the patient, indicates n complete upper motor neuron lesion. Strain and Crede micturition both indicate a lower motor neuron lesion. In this case the patient has to strain ab- dominally or requires manual suprapubic pressure in order to 208 ADVANCES IN DIAGNOSTIC UROLOGY void. Tlie comis is tlie level at Avliich the spinal motor supply of the urinary bladder originates, and all lesions above the le\el of the conus from the second to the fourtli sacral segment result in an upper motor neuron lesion of tlie urinary bladder, nhereas those of or lielow the conus result in a lower motor neuron le«ion of the urinary' bladder. If the desire to void is pre«ent, tlie lesion is incomplete; if it is ahseni, the lesion is usually complete. Interruption (inhibition) of miclurition (normal, paradoxical, passive) reflects tlie extent and level of the lesion. If the patient can interrupt his urinary stream at will, the nerv’e supply to the bladder and especially to the striated pelvic floor muscles may he considered normal. If there is paradoxical interruption of mic- turition (involuntary Iransieiil interruption of the urinary stream during refiex voiding), then an upper motor neuron lesion is to be e.\peclcd. Passive interruption of miclurition (interruption when the patient stops straining) denotes o lower motor neuron lesion. Divitnal and nocturnal enuresis are significant only if they persist lieyond the age of eight or ten years. If enuresis lias per- sisted from Iiirtlt, it may Iks associated with a congenital neurologic disorder or hirth injury to the central nervous system. Diurnal enuresis may occur with any type of urinary incontinence. Noc- turnal enuresis may be of psychogenic or neurogenic origin. The hi'-tory of the use of a catheter, leg urinal, or appliances will help to date the on«el of the neurogenic bladder when this cannot be ascertained otherwise. TIic management of an indwell- ing urethral catheter (daily irrigation and frequency of change) should he recorded. Whereas the presence of a catheter indicates imbalanced bladder function, the u'e of a urinal indicates balanced function but some type of incunliiience. Neither catheter nor urinal is pathognomonic in regard to level or extent of the le«ioii. ^'etirologic Urology 209 TYTE OF INCONTINENCE Precipitale miclurilion is cliaraclerislie of an incomplete upper motor neuron lesion, or an ^Vnintnbited neurogenic bladder.”*^' It occurs •with brain lesions, for example, with stroke, and with partial spinal cord lesions. Psychologic incontinence can occur after lobotomy. The lobot* omized patient retains the desire to void and has inhibition (the ability to slop miclurilion), but he does not care to stop it under socially unacceptable conditions; for example, he voids on the floor. Stress incontinence is cliaracferisiic of a louer motor neuron lesion. Laughing, cougliing, lifting, and walking upstairs or do'jvn- slairs are samples of stress incontinence in the absence of obstruc- tive uropathy. Stress iiicontinence is either neurologic or muscular. The neurologic form is connected with a lower motor neuron lesion of the detrusor and of tlte striated muscles of the pelvic floor; it has been referred to as “autonomous bladder.”®’ **' The muscular form is due to a damaged pelvic floor musculature. Overflow incontinence can occur in patients with an upper motor neuron lesion or a lower motor neuron lesion with acute urinarj* retention. The lesion can Iw eilJjer complete or incomplete and still lead to overflow incontinence. Reflex incontinence, sometimes called “neurogenic reflex bladder” or “automatic or normal cord bladder,” occurs in patients with upper motor neuron lesions. Incontinence of nonresistance or “dribbling” is found in patients with an upper visceromotor neuron lesion combined with a lower somatomotor neuron lesion, i.c., spina bifida (with a spastic de- trusor and a flaccid pelvic floor). Such a condition may be sur- gically induced by transurethral resection ol the internal and external urinary sphincters. 210 ADVANCES IN DIAGNOSTIC UHOLOCY DOWEL niSTORY Frequency of defecation enters into ll\e diagnostic picture. If existing for a very long period, abnormal frequency may suggest that a psychogenic disturbance rather than a recent neurologic disorder is one of the etiologic factors. Tlie desire to defecate parallels the desire to void; it travels essentially by tlje same patluvays. Tlierefore disturbances of def* ecalion, like those of micturition, make a neurologic evaluation necessary. The differentiation of gas or fecal matter in the rectum indicates an undisturbed autonomic nerve supply to the rectum and n functioning condition of the sacral nerve segments. Sensation of fecal matter passing the anal canal can he com* paced u'ilh the sensation of urine passing through the urethra. It is associated vvith tlie presence of exteroception of touch and iem* perature in the anal mucocutaneous junction, and proprioception in the musculature of the pelvic floor. If the patient has to use suppositories, digital rectal stimulation, or other means to initiate bowel movements, be may linve either an upper or a lower motor neuron lesion. Becau^^e this condition cannot he determined by the bistor)’ alone, the type of lesion can be ascertained by digital rectal examination. A slow, writhing contraction of the internal anal sphincter and a patulous, fiacrid action by the external sphincter characterize a lower somato- motor neuron lesion. A spastic contraction of the external anal sphincter denotes an upper somatomotor neuron lesion. If a patient with diarrhea is incontinent of his stools, he may suffer either a complete or incomplete, upper or lower motor neuron lesion. Patients with well-regulated bowel function hut with complete or incomplete, upper or lower motor neuron lesion are not necessarily incontinent. I'lfeurotogic Urology 211 SEXUAL mSTOHY OF THE MALE Patients willi complete upper motor neuron lesion have reflex erections; those with incomplete upper motor neuron lesion have either psychogenic or reflex erediona. Patients with complete lou’er motor neuron lesions liave exclusii'ely psychogenic erections. Reflex erections are elicited hy manipulation of the genitalia, such as cleansing the genital region or changing a catheter. Erec- tions arc said to result from impulses coursing along the para- sympathetic (pelvic) nerves (nervi erigenles) from the sacral segments. However, persons with lower motor neuron lesions wlio do not have reflex erections or impulses along tlie parasympathetic nerves may still liave psychogenic erections. These result from impulses originating in the brain and are probably mediated liy tlie ihoracolumhur autonomies (orthosympathetics). Psychogenic erections occur not only with incomplete upper or lower motor neuron lesions, hut also with complete lower motor neuron lesions (i.e., destruction of conus or cauda equina). A reflex erection may occur in iiornial males or in patients with a (complete or in- complete) upper motor neuron lesion. Complete impotence may be psychogenic or it may he organic, as in patients with complete lower motor neuron le'^ions (more frequently) or in those with complete upper motor neuron lesions (less frequently). Ejaculation is usually absent in patients with complete upper motor neuron lesions, although rare exceptions do occur. It is also alisent in those patients with complete lower motor neuron lesions who have no erections. Ejaculation is more frequent in patients with lower motor neuron lesions who have psychic erections than in those with upper motor neuron lesions who liave reflex erections. Orlliosympathelics and somatics are necessary for physiologic ejaculations. Emission (the visceromotor twmponent of ejaculation) results from impulses mediated hy the ortbosympathelic nen-es. It rarely 212 ADVANCES IN DIAGNOSTIC UnOLOCY occurs in patients with upper motor neuron lesions, hut it occurs not infrequently in patients with complete lower motor neuron lesions because the orthosympathetic outflow is partly or com* pletely intact when the lesion is l»elow the lowermost thoracic or upper lumbar segment*. Integrated contraction of the Inilbocareniosus and ischiocaver- nosus muscles (somatomotor component of ejaculation) results from impulses mediated by the pudendal nerves. It occurs rarely in patients with upper motor neuron lesions Ijccausc the eliciting stimulus of emission is absent. It does not occur in patients with lower motor neuron lesions because of the damaged somatic sacral outflow; In such ca«es sexual secretions drjhl)le from the urethra, a process called flaccid ejaculation. Orgasm is lost in patients who have a complete upper motor neuron lesion. All variations and degrees of orgasm, includivtg no orgasm at all, are experienced by patients willj lower motor neuron lesions; they have erections and emissions, and experience a variety of pleasurable, though occasionally p.-tinful, sensations or equivalents of orgasm. Lo'ss of orga«m may occur also with psycho- genic disturbances. Orgasm is lo>.l after bilateral chordotomy, and occasionally after unilateral chordotomy. Impotentia coenundi (loos of ability to perform inlerroiirsc) may be caused by com- plete loss of erection or by unsustained erection. Impotentia generandi (sterility, but not necessarily infertility) may be a consequence of absence of emission, premature ejaculation, or regurgitation of ejaculation. SEXUAL III S T O K V OF THE F K M A I, E Dyspareunia can he of either psychogenic or organic source, such as tight hymen or small vagina. It has not been ohvcrved in patients with any type of cord lesion. Frigidity is not suggestive of a neurologic disorder; rather it is usually of psychogenic ^’eurologic Urology 213 origm. Lack of orgasm is also usually of psycliogenic origin, unless neurologic deficit can l>e demonstraled. Orgasm in both sexes involves t!ie simultaneous nervous discharge of all three components, the somatic, orthosympalhelic, and parasympathetic nervous systems. UllOI.OCin 1‘ROCEDORES Tlie ice water test consists of instilling 2 ounces of sterile ice ^s'ater into the empty urinary bladder through a 16 Frencli whistle- tip catheter. In a neurogenic bladder due to an upper motor neuron lesion, eitlier the catheter and the ice water or tlie catheter alone is forcefully expelled within a few seconds. In a nonnal bladder or in a neurogenic bladder due to a lovs’cr motor neuron lesion, lljere is no response to the instillation of ice water. A cystometrogram with eitlier the Lewis aneroid cyslometer or ll )0 simple water manometer, essentially consisting of a glass lube witii a yardstick taped to it, can give only the present status of the paliejifs neurogenic bladder; it is not in itself a diagnostic or prognostic tool. Retrograde cystometry', practiced with extrinsic increments, is less pliysiologic than e.xcrelory’ cystometry, with urine supplying the volmne.® It docs, however, j>ermil evaluation with regard to palliologic autonomous or uninhibited waves. For interpretation the slope of the curve (basal tone) and iIjc shape (waves) have to be considered in conjunction with other clinical tests. Four tilings should l>e recorded on llie cystometrogram: (1) the patient’s first dc>ire (o void, (2) his first painful desire to void, (3) severe pain from suppressing micturition, and (4) the attempt at straining. Generali)- speaking, if cystometry' is per- formed in the ah^^ence of spinal shock, there are tendencies of a .'^hift to the left m upper motor neuron lesions, and a shift to the tight in lower motor neuron lesion«. If done during periods of spinal shock, cystomelrograms of patients with upper ami lower 2M ADVANCES IN DIAGNOSTIC UROLOGY motor neuron lesions look alike, and they not infreejuently re- semble lliose ‘•een in palienls witli lower motor neuron lesions, i.e., they show a shift to the right. The sphiticteroinelrogram i» of limited use, low values being obtained in palienls with lower motor neuron lesions (below 20 to dO mm. Ilg) and normal (80 to 100 mm. Hg) or high values (ISO mm. Hg oi more) in patients with tipper motor neuron lesions. The spliiiicteromelrogram pai- allels the findings of the hulhoca\emo"U> rellev and unal sphincter tone. The delajed cystoiirelhrogr.nn docs not disclose dilTerent tyjies of neurogenic bladders because the bladder outline can change with the duration of the condition, eventually making u diagnostic distinction impossible. The condition of the vcsical neck, cellules, and diverticula and the size and contour of the hhidder can all be evaluated by lliis teclmique. Vesicoureteral reflux of urine is less common in patients with lower motor neuron lesions than in tlio«e with upper motor neuron lesion*. The voiding cystonielhrogram permits a comparison of the present function with the known physiologic pattcni.^ It will also detect whether tlicre is relhix only during the net of micturition. Cim-radiogniphy, fluoroscopy of voiding, or a voiding rystonre- throgram shows the dynamics of urinalinn and foci of dysfunction. Spastic external urinary sphincteis can lie seen to open and clo'c with uncontrolled rajiidity. The pelvic floor is seen to contract rapidly and elevate itself in a haphazard pallem. Under fluoroscopy «ipa«tic coiilraclioii- of llic detrusor muscle can aho he noted as rapid and irregular, and the bladder axis as more vertical and concentric. When a patient with a lower motor neuron lesion is fiiioroscoped, minimal contractions arc seen in the liypoactivc or flaccien<}eo<n or neuromuscular dis- tuibanee of the detnisoT, Neurologic Urology 217 seconds, and the second enrve is steep, wiifi a catlieter voiding time of 20 seconds for the same volume, a bladder neck obstruc- tion exists (Fig. 3). If both curves are flat, indicating a slow voiding pattern, a neuromuscular disturbance of the detrusor may exist (Fig. 4). Intravenous urography must be studied periodically to deter- mine the status of the upper urinary tract. Regressive changes in the kidneys or ureters occur with both upper and lower motor neuron lesions; occasionally they are observed in the presence of a well-halanced bladder function. Anomalies of the bony spine and the scout film of the abdomen should he evaluated. Tlie ratio of residuum to bladder capacity is an important de- termination. Tlie residual urine is measured one hour after removal of the catheter and is compared with llie spontaneously voided volume. Twenty per cent of residual urine is compatible Figure 3. DifTercnlial uroflogranis demonstrating bladder neck or other in{ra\esical obstruction; unobstructed pattern (o) when patient voids through a catheter; with tbe catheter removed, obstructed pattern (b) when patient voids at a slower rate. 21 « ADVANCES IN DIAGNOSTIC U It O L O O Y Figure 4. DifTercntial uraHograins showing drtrusor weakness on a neuromuscular basi«. Doth (at ami (b} indicate impaired voiding rale*. with a balanced iilaJder function of patienlv vvitli upper motor neuron lesions; h Is 10 per cciil in pjlicnt» with lower motor neuron lesions. The respective minimal capacities are 250 and 350 milliliters. Cystoscopy will indicate tralKrciiblions, cellules and diverticula in both upper and lower motor neuron lesions of long siaiiding. Nonopaqiie stones, not seen on roentgenograms, will he found. The conditions of the vesical neck can he assessed. The sensihility of the bladder imicosa, including dome, fundus, trigone, lateral walls, and ureteral orifices, is tested hy lightly toucliing the muco'a with a ureteral c-atheler or with the wire of a Timherlake electrode. The physiologic response to this stimulus is 2 >ain.“ In the correct lateralization the inUieiit recognize* promptly whether the right or left side wall (or orifice) has Iwen stimulated. Sacral segments bUjiply the trigone, with an additional overlap from llic thoraco- lumbar segments which supply the lateral walls, dome, and ureteral Neurologic Urolof'y 219 orifices. Mucosal perception ceases llirouglioiit lire liladder if the lesion is above tlie eleventh or twelfth thoiacic segment. If the lesion is Iielow tiial level, dome, side walls, and orifices may still perceive stimulation, imt the trigone docs not. Incorrect lateraliza- tion indicates damage to the thoracolumbar segments. If the response to stimulation is not pain Imt only a vague sensation, damage to the respective pathways may he assumed. Laboratory data, including urinalysis, culture, complete blood count, creatinine and blood urea nitrogen determinations, serve the same purposes as in general urology”. In cases of upper motor neuron lesions, topical Pontocaine anesliiesia of tiie vesical mucosa is used to restore Itladder func- tion by altering the pattern of the leflex arcs between mucosa ami detrusor, mucosa and pelvic floor mu«cnlalnre, and tbe feedback reflexes; detrusor to detrusor and pelvic floor to pelvic floor.® ® Immediately after determining ibe ratio of capacity to residuum, 2 to 3 ounces of a 0.1 to 0.25 per cent aqueous Pontocaine solution Is introduced into the empty bladder and dr.tined after 10 to 20 minutes, The catlieter is tlien removed and the residual urine is tested after 1 liour and after 24 hours. If tliere is no beneficial result, i.e., improvement of l)ladder function, llie lest can be re- peated after 2 or 3 days. It can !»e done witli impunity 2 or 3 limes per week. Pudendal nerve anesthesia'* is used in patients with upper motor neuron lesions in order to improve bladder function by cbangiiig tbe pathologic reflex palleni between detrusor and pelvic floor musculature, and to establish the noinialiy reciprocal relationship whereby one structure relaxes while the other contracts and vice versa. The patient is made to lie on his abdomen wifli a pillow under In’s hips. The sacrolnbeious ligament and the ischial tu- berosity are 2 landmarks for the infiltration of 10 cubic centi- meters of 1 per cent Xylocaine or 10 to 30 milliliters of 1 per cent Intracaine on eacli side. Details of tbe Iccbniijue are described 220 ADVANCES IN DIAGNOSTIC UnOLOO' elsewliere.^ If only temporarily successful, tlie teclmique niu<;t L« repeated before a permanent neurotomy is contemplated, a pro cedure indicated only in rare and exceptional cases. In patients Avitli upper motor neuron lesions, dilTerential sacra iierre ane'lliesia’® is used for improvement of bladder function especially in tbe presence of a hyperactive detrusor. The technique has been described in detail.' Anesthesia can be repealed ant must precede a contemplated iien'e section, e.g., when being con sidered to relieve pain from Hunner's ulcer.^' When single ane«thesia is ineiTective, a combination such im Pontocaine-pudendal or Pontocaine-sacral may, in very rare in stances, be successful. NEUItOLOCIC EXAMINATION No one expects a urologist to be an accomplisltcd neurologist; ncterthclcss, be must acquire a minimiiin amount of knowledge in order to correlate the findings of the urologic examination (cyatoscopic testing of tbe scnsibilUy of bladder mucosa, cystom* etrj‘, ice o-ater test, and the other techniques discussed) with the findings of a sy«lcinallc neurologic examination. The urologist mu«l knou, for example, that an upper motor neuron legion (central lesion) is accompanied by hyperactivity of llie deep tendon and muscle reflexes, skeletal mu'^cle spasticity, and pathologic linger and loc signs (Holfman, Ilabinski), and that a lower motor neuron lesion (peripheral lesion) is charac* terized by absent deep tciuloii or muscle reflex activity, skeletal mu'-cle flaccidily, and absent pathologic toe signs, Allliougli the urologist’s interest focu«cs on the activity of the conus, the re«l of the neurologic inventory is of importance. Lesions nbo\e the conus prorlucc an upper motor neuron lesion (supraseg* mental) in rcganl to bladder function; lesions of or below llic conus arc followed by a lower motor neuron le«ion (segmental or Neurologic Urology 221 infrasegnicnlal). TJje evaluation of the rectal sphincter tone and of the ana] and l>ulbocavemosus reflexes permits a differentiation between conal activity and inactivity. A patulous anal sphincter indicates conal inactivity (from the third to the fifth sacral seg* menl), whereas a strong sphincter tone denotes the opposite. The degree of volitional contraction and relaxation must he assessed when it is present. A simple rectal digital eacnmination can thus provide a lead. The anal reflex, occurring at the fifth sacral seg- ment, is elicited by applying a pin prick to the mucocutaneous junction; a visible sphincter contraction follows if the reflex is positive. The bulhocavernosiis reflex, centered between the fifth lumbar and fifth sacral segments, is elicited by gently squeezing the glans penis, stimulating the urethral mucosa, or stimulating the vesical mucosa by a brisk yet gentle pull on an indwelling Foley bag catheter. Tlie positive response consists of a brisk contraction of the anal sphincter, felt by the examiner’s finger introduced rectally. In addition to tiiese examinations, a general neurologic examina- tion is not beyond the scope of the urologist. Examination of cranial nerves and of motor and sensor)' function of the body, the importance of which is obvious, can be readily accomplished. For example, if tlie examiner finds that llic reflex activity of the patellae (at the second to fourtli Iuml)er segments) and of the Achilles tendons (at the fifth lumbar to the second sacral segments) is exaggerated, he may be led to believe that he is dealing with an upper motor neuron lesion. But if lie ascertains that other reflexes, such as the biceps (at the fifth and sixth cervical segments) and triceps (at the sixth and seventh cervical segments) are equally exaggerated, he may assume that the general trend to increased reflex activity may, in the absence of other pathog- nomonic neurologic findings, be of psycJjogenic ratlicr than neuro- genic origin. As anollier example, absent patellar and ankle reflexes with flaccid paralysis of the lower extremities and absent plantar reflexes (at tlie first and second sacral segments) at first 222 ADVANCES IN DIAGNOSTIC UROLOGY suggest a lower motor neuron lesion; but if the patient reports reflex micturition and the bulliocavemosus reflex to be positive, then the segments below the second sacral are still functioning, and the patient may be suffering from the sequelae of a partial cauda ey fibers in closest proximity to the spinothalamic tracts of the lateral coUimits, whereas the sensation of bladder dislenlion is said to be conducted by both the lateral and posterior columns. It is apparent, tlierefore, how important it is to correlate the segmental dermatome deficit with the urologic symptom^ and signs, which are eillier recorded in the patient’s history or actually found in sensor)* studies of the Idadder mucosa (c>’stoscopicnl!y) or of the bladder muscle (cyMomelrically). RnPEKHNCRS 1. Dors, E. Neurogenic bladder. Urol. Surv, 7:177, 1957. 2. Dors, E. Topical anesthesia of the vesical muco«a ns s tool for the management of the neurogenic bladder. /. Vrol. 79:131, 19.50. 3. Bors, E. !!., and Winn. K. A. Spinal reOex aclivil) from ll«* %e«ical mucosa in paraplegic patients. A.M-A. Arch. Sftirol. Psychint. 70:339, 1957. 4. Dors, E., Coinarr, A. E., and Moullon, S. H. The role of nerve blocks in \be management of traumatic curd bladders; Spinal anes- thesia, subarachnoid alcohol injections, pudendal nene aiieslhe«ia. and vesical neck anesthesia. /. ffrof. 63:loscoplc patiiology has long challenged scientists interested in endoscopy, optics, and photography. Nitze and Leiler's introduction of a cystoscopc willi an optic system in 1887 was tlie beginning of urologic endos* copy. In 1894 Nitze made the first attempt to photograph the interior of the urinary bladder. Tlie: (1) clear, interchangeable lenses which permit sharp focus and through-the- lens viewing of the photographic field; (2) a small, ct)mpacl camera body which is rigidly fixed to llie lens system, has a 22t Advances in Cyslopkolography 225 Figure t. Early cjstoscopic camera with a revolving drum cassette, probably developed bj Dr. Max Nilze. (Armed f'orces ISTedical Museum Instrument Collection.) variuble sliuUcr, and permib rapid loading of eidter black-and- white or color films; (3) a brilliant light source having the correct color temperature and providing adequate illumination of the photographic field vvitliout injurious electric currents. McCrea'^ introduced in 1941 the first practical unit for still intravesical photograpliy. A lens system of his oum design was placed in the standard 24 French Brown-Buerger cystoscoptc sljeath. A refiex mirror in the camera hox also acted as the shutter and permitted actual observation of the photographic field until Figure 2. Early c}.sl««cop5c campro dcveloj»efl bj Louts and il. Loewen- stein, Berlin, (Armed Forces Medical Museum Instrument Collection.) 226 ADVANCES IN DIAGNOSTIC UDOLOCY Figure 3, Enlargement of the ocular end of the Loevven»tein camera; the empty film ca»»ette h in the foteground. the pliolograpli tvas made. Tlie original picture:* \>erc made on orthochroniatic film. In 1913 he modified Ids original equipment to jicrmil color photography.^ The sheath was enlarged to 28 French to accom- modate a special 21-toIt, O.S-ampere lamp. A po>\cr unit was constructed mIucIi reduced 110 A.C. to 12 volts. At this voltage tlie lamp permitted examination of the vesical cavity. A liming device was placed in a second ciraiit of 2i volts which coulil he activated hy a throw .switch. Tluis the tnaxinutm ilhmiinatioii ua- produced during a timed exposure period. Kodachroint* Type A, 35-millimcter film was used. Tlie average lime required was HO to 3 .seconds, depending upon the illumiiuilion, Tlu* equipment v\as grounded to the cysUe-copic table to prevent discomfort to the patient in the event of a short circuit. Hanley’ in 1959 evaluated the new German Sass Wolf cy.sto- scopic camera, which is similar to the McCrea instrument. Ilhi- Alliances in Cyslopholofraphy 227 minalion is obtained from a special lamp burning at 12 volts. When the shuller of tlie camera is released, a synchronized 24'volt flasli cuneiil gives a brilliant flash. A special reflex mirror adapter is used for through-tlmdens viewing. The problem of achieving adequate illumination of the bladder to permit color endopholography with slow-sj>eed, fine-grain film is still unsolved. To pronde sufficient illumination, l)igh voltages, ^vhicli could be dangerous to (he patient, must be placed on the small endoscopic lamps. It lias been known for many years that light may be transmitted along transparent glass, lucile, orrpiarlz rods. McCrea^’ and others have utilized a quartz rod 2.75 miUhneters in diameter to trans- mit tbtough an endoscopic sheath brilliant light from a large Figure 4. Fiber Optic light carrier (with Us power supply) and the Fiber Optic c>sln5Cope sheath, developed by American Cystoscope Makers, Inc. The5c instruments, together with llie Vest lens sjslem, are placed in the resectoscope shown in the foreground. 22a ADVANCES IN DIAGNOSTIC unOLOCY extenial bulb. Tliis lamp is cooled by a blower system. An auto- matic film-advancing camera with an external reflex-viewing unit ^vas part of McCrea’s equipment. American Cystoscope Makers, Inc., has developed a unit in which a brilliant, c.xtemal light source is transmitted through a flexible Fiber Optic light carrier to a new Fiber Optic cystoscope sheath. This special sheath acts as a light carrier and surrounds a Vest lens sjstem. Thus circtiinferential light is transmitted to the ohjert for maximum iHumination (Fig. 4). This unit may he used ^^ilh a through-the-lens reflex 35-miUimeler camera or with a reflex motion picture camera. I introduced in 1961 an endoscopic camera which utilizes existing cj’stoscopic equipment coupled to a Minox III-S camera (Fig. 5).*^ A large McCarthy view ing telescope with a photographic lamp (A.C.M.I. 50 amp.) is introduced into tlic bladder ihrougli a 24 French resectoscope sheath. Tlie lens system is attached to Figure S. C)slosco{UC camera which comliincs a targe McCarthj fore- oblique viewing lens willi a 50-amp. lamp, a teaching element, and the Minox III-S camera attaclietl b) the Mioox Dinooular Attachment. Advances in Cyslopholography 229 the double ocular teaching clement, thereby permitting continuous reflex viewing of the photographic field. The Minox III*S camera is fixed lo the main viewing ocular by the Minox Binocular Attach- ment (Agfa color H or % second at F 3.5). ClNECYSTOPtlOTOCIlAPIIY The technical problems in developing cinecystopholography have ))een similar to those in developing still techniques. Recently many fine through-the-lens refiex 8- and i6-mil}imefer cameras have become available. These cameras may he directly altaclied to the photographic lens ayslems to provide a clear view of the bladder during photography. Adequate illumination is again the most difficult problem. McCarthy and Ritter^ used an external light source transmitted through a quartz rod. When this light source was coupled to a Camex 8-mlllimeter or Bolex 16-millinieler reflex camera, clear films could be made at speeds of either 8 or 16 frames per second, depending upon the working distance from tlie objective lens to the ol)ject. Shimizu in 1961 developed a very intense light source presumably from a flashing endoscopic lamp. The unit is cycled for use in cinecyslopholography with his wide-angle lens system. I have uicd a heavy filament lamp on a right-angle and fore- oblique photographic lens system and a Camex reflex 8-miIli- meler camera (Fig. 6). With Ektachroine E R Type B film, adequate exposure is obtained at 16 frames per second. However, this very fast film has a considerable amount of-grain. Kodachrome type II-A, altliough slower in speed (8 frames per second), gives less grain and sharper films; the films may he enlarged to 16- millimeter with xcry little loss of definition. Wijen using a speed of 8 frames per second, care must be taken to prevent motion and to allow enough footage for cacli sequence. 230 ADVA.NCES IN DIAGNOSTIC UROLOGY Figure 6. A cinec)s(op]iotogra|>hic s)$tm 1)> A.C.M.I. which utilizer a large McCarlli) fore-ohUque viewing lens with an A.C.M.I. S0-am|i. lamp and a large righuangle photographic c)s(o«copr with a hea\}* newed during die past decade by the discovery of the chromatin body and its prolinble relationship to chromosomal abnonnalities. TJierc have also iiccn developed new teclmlques which will ulti- mately aid in identification of specific cliromosomol deviations. Following the serendipitous finding that nuclear sexing could he performed, Barr* quickly moved to the problem of human inter- sexuality; following his lead many investigators lliroiigliout the world began to report clinical applications of the test. Among other findings, females with Turner’s syndrome were reported as chroma- tin negative, males with KlincFcller's syndrome were found to he chromatin iiositive, and true intcrsc.xes were found to be cillicr chromatin negative or chromatin positive. Because the ability to recognize and classify chromosomes has been combined with progress im I'erfcCting tiMbIAc tedmiques lor cnlvuiing VrrrmBYi cells made by investigators employing tissue culture metIuKh, the chromosomal constitutions of some of the mo?t puzzling ca'cs of intersexuality have l»ecn made known. All of this ferment has whetted the intellectual appetite to learn more about liunian inter- sc.xualily. 232 Diagnosis of J/itersex Problems 233 CniTERIA OF SEX Comprehension and appreciation of the concept of intersexuality requires some knowledge of the morphologic and psychologic criteria of sex. Most persons writing on tins subject enumerate five morphologic and two psychologic criteria. The five morpho- logic indicators are the chromosomal or genetic sex, the gonadal sex, the external genitalia, the iuleriial genitalia, and the hormonal status. The chromosomal or genetic sex of the individual is established at the time the ovum fertilized hy the spermatozoon hearing either an X or a Y chromosome. Tims the sex chromosomal con- figuration of the human female is XX and that of the male XY. Severinghaus^^ in 1942 was able to identify the 47 autosomes and the allosomes XY in tlie testicular material from a patient with intersexuality, and thereby established tlie patient ns a genetic male. The complexity of the technique did not allow its widespread application to clinical cases until 1950, wlien Harr and his associ- ates were aide to show that it was possible to determine the sex of an individual by study of the nuclear chromatin body present in somatic cells of the l;ody. Further studies have indicated that in some instances it is now possible to equate the chromatin sex with the chromosomal sex of llie individual. The gonadal sex of tlie individual is established by the evolution of the hipotential gonad into citlier a testis which produces sperma- tozoa or an ovary winch gives rise to ova. Such development pro- ceeds under the influence of the genetic constitution. The gross mor- phology is not u.sed for determination of the gonadal sex; such sexing must he ha‘>ed on the histologic architecture of the gonad. Tlie external genitalia, presumably differentiated under gonadal influence, arise from eniljryonic hipotential anlage which readily explains the amiiiguous genitalia of some patients with inter- sexuality. Although often used by the obstetrician for assignment 231 ADVANCES IN DIAGNOSTIC UROLOGY of sex, ihe morpliologj' of the externa] genitalia is the least reliable criterion for such i;riNiTiON5 Interscxualhy exists ia a patient when one or more contradic- tions of the morphologic rriteria of sex are found. The sc.x of rearing and the gender role arc not appliRihlo, iUofc intersex (male liennajihiodilism) indicates that tiic patient Diagnosis of Intersex Problems 233 with intersexuality has gonads whicli are testes and the chromatin test is negative. (The terms hermaphroditism and pseudoherma- phroditism are gradually giving way to the expression of *‘inteisex.”) Female intersex indicates that the patient with intersexuality has gonads which are ovaries and the chromatin test is positive. True intersex is applied to those individuals who have histologic evidence of both testicular and ovarian tissue, and wlio may or may not have contradictions of the morphologic sex criteria other than gonadal. Conadal aplasia indicates the congenital absence of gonadal tissue. Gonadal dysgenesis indicates congenital faulty development of the gonadal tissue, which, however, can be identified as testicular or ovarian on the basis of germinal and sustenfacular elements. Sex reversal is a term used by experimejttal embryologists to indicate a state in which the gonad resemldes a sex which is opposite to genetic intent. The use of (he term in clinical situations is ambiguous and cottfusutg iu (hat it implies a process already initiated and tlietr reversed (apparently never the case in human material). Faulty gonadogenesis, as far as can be determined, results from varying degrees of development of the cortex and the medulla of the primitive gonad and not from retrogression from a previously dilTerenliated state. Krebs’s classificalion of true intersexes has been abandoned as too complicated. However, since cases in the literature are classified in this manner, the terms used are as follows: bilateralis indicates that ambisexual t/ssue i> present on boCli sides of the Iiody; unilateralis that amliiscxual tissue is present on one side of the body; lateralis that male gonadal tissue is piesent on one side and ovarian tissue on the other; completus that gonadal tissue is present on both sides of the body; and incompletus that gonadal tissue is absent on one side. Table 1. Classifcalion of Inlersexes KImrfclirr's »TTnIrof Diagnosis of Intersex Problems 237 CLASSIFICATION OF THE INTERSEXES In tlje dassificalion given in Table 1, the chromatin test and the gonadal sex are used as nosologic determinants. Tliis classifi- cation parallels the procedures listed in Table 2, u’hich is an Table 2. Is This a Case of Inlersexuality? E\alu3te th« morphologic criiem of sex by pliystcal findings, radi- ography. eny. Iaborator> studies and chromatin lest Coniradiciion of sex crilerta indicates inlersexuality iVfgattie- i. Male iniersex (gonads •= testes) 2. Conadal aplasia Bonnes ie-Ulltich syndrome Turner’s syndrome 3. Gonadal dysgenesis (gonads =» ovaries) ^Jrue htenri^ Testicular and otamn tissue ^Potime Female intersex (gonads * ovaries) a Adrenal hyperplasia h Drug dunng pregnancy c Aiaternat ovarian tumor (]. Idiopathic Gonadal aplasia (gonads absent and male genitalia) Gonadal dysgenesis (gonads «= testes) a. Adult (fCIinefelier) h Childhood outline for attack upon a suspected case of intersexuality and represents tlte major differential dmgnoses. Tltree main classe-s evolve: Class I is represented by those cases in which agreement exists bettveen the cliromatin and tlie gonadal sex. Class II is 238 ADYA.NCES IX DIAGNOSTIC UROLOGY composed of lliose cases in wliich disagreement cyisIs between these criteria. Class III includes tliose cases in wliicli the nature of the chromatin te't can l)e detennincd but in wliich there Is no evidence of gonadal sex. \^nieTe possible, for those disorders which bear the appellation syndrome, the appropriate tenn, such as Turner's syndrome, will l»e used; those terms are well established in the literature and there is little to be gained by introducing a whole new set of designators. However, several cases have been reported which bear no such ubiquitous connotation of syndrome, as, for example, chromatin negative gonadal dysgenesis of child- hood in Class 11. Hutchings*' has reported such a case. Similarly the (lesignalion childhood rArome shown, there is no intersexuality. Indeed, a masculine person who has no contradictions in the morphologic criteria of sex but whose Diagnosis of Intersex Problems 239 gender role has been that of a female might erroneously be thought of as an intersex problem. Some cases of intersexuality do not present themselves as problems in sex determination and are discovered only by a high level of clinical diagnostic acumen; thus die obvious fades into the not-so-obvious. It is not always possilde to a«sign the sex of a newborn child as quickly as anxious parents and relatives would wish. It is belter to have them wait a few tense weeks than to commit an infant to a life of misery by decisions bom of baste and mis- information. Diagnostic aids useful to the physician are pertinent historical facts, significant signs elicited during the physical examination, radiographic and endoscopic examinations, laboralor)’ delermina- lions, surgical explorations, and microscopic examination of properly fixed gonadal tissues. Special attention in taking the history may profitably be given to inquiries about the patient's siblings or blood relatives who may have had problems suggesting intcrse.xualily. For example, some obsei-vera liave reported family studies in which several sililings have had sucii problems, and 1 personally know a family in wliich three young sisters all hove male intersexualily. Inquiry about the use of progestins or androgens during pregnancy may estahlish the etiology of the intersexualily since there is fairly widespread use of progestins in cases of threatened ahorlions. ICnowledge of maternal ovarian tumor during pregnancy would obviously be of diagnostic importance. Physical Examination Among the physical abnormalities which might lead a physician to consider a diagnosis of intersexuoUly are eunuchoid proportions of the body, short stature, height above the normal expectancy in hoys, greater span than heiglil, webbed neck, lack of lieard, “fur- cap” distribution of head hair, hypertelorism, mongolism, gyne- comastia, inguinal hernia in girls, abnormal masses in the genital 2-10 ADVANCES IN DIAGNOSTIC UROLOGY labia (one patient complained of lumps in this area which “gel in the way when I dance with a man”),* disturbances in pubic hair configuration, ambiguous genitalia, hypospadias, bilaterally undescended testes. The presence of ambiguous genitalia, par* ticularly in infants, accompanied citlier by hypertensive or salt- losing states, are highly suggestive of female inlersexuality due to congenital adrenal hyperplasia. In some infants, edema of tlie hands and feel or cutis laxa may be indicative of the Bonnevie- Ullrich syndrome. Radiographic Findings Radiography of the lower urogenital tract will supply additional evidence for inlerpretalion of llic abnormalities know'n to be pres- ent. It Is common practice to place the patient in the scmilatcral position on tltc radiographic table and then, if possible, to catlie* lerlze the urethra and leave a retention catheter in the bladder. Air is injected into the bladder and, while the radiographic film is being exposed, a radiopaque jelly is rapidly injected into the uro- genital orifice. In interpretation of the film, the contrast medium u«ed will aid the physician to determine Uic structures portrayed. In other circumstances I have found it useful to provide an addi- tional small opening below the balloon of a retentive-type catheter; after the urctlira lias been cathclcriied, the balloon is distended, slight traction is a]>plied, and a radiopaque Iluid is injected into Uic catlicler. The radiograph thus obtained W’ill oiiUhie the bladder and any anomalous genital structures arising from the ureUira (Fig.l)- Cysloscopie Frn/Mrc» Witli the panendoscope the phj’sician may confirm the interpre- tation of the films or provide direct visualization of the uro- genital tract when radiographic fuidiug^ are inconclusive. MTicn, * ThcM lump) provei] to be le«tn o( nonaU «Ur. Diagnosis of Intersex Problems 211 Figure 1. A roentgenogram showing the bladder filled with radiopaque fluid and the vagina arising horn the midportion of the urethra. One oviduct is also depicted. A relenlion catheter with openings above and below the balloon was used; slight traction Avas applied on the catheter as the fluid wa* injected. occasionally, the genital tract is not entered hy the radiopaque material, endoscopy will discover such a failure. It lias been the ratlier routine practice in our clinic to use the panendoscope together with radiography in all suspected cases of intersexuality, iMhoralory Tests Laboratory studies which can be used routinely are the chroma* tin test and the determination of IT-ketosleroid and gonadotropin 212 A-ttVANCES IN DIAGNOSTIC UKOLOGY excretions in a 2Hiour sample of urine. Tlie level of IT-kcto- steroid excretion in the urine is elevated in normal infants and in infants witli female inlersexualily due to adrenal hyperplasia during the first 3 ANceks of life. TJic determination of the presence of urinary pregnanelriol or pregnanetriolonc will he helpful where such a di^wdered adrenal stale is suggested, for these suli^lances are not found in the urine of a normal infant. Tlie suppression of ele^nled IT-ketosteroids hy conisniie or the excretion of nrin.iiy pregnanelriol or pregnancltiolone is indicative that the suspeiied case of inlersexualily is due to congenital adrenal hyperplasia. The level of gonadotropin oxcrclloii has little clinical importance \u cluUlren, Wt \t 1% usually elcvatcy biopsy. Later Moore and Barr de«crilicd the oral smear method nhicli is widely ii«ed today. Cells of the vaginal mucosa, urinary >cdimenl, and nmniotic fluid have been «uiila!ile for study. David'-on and Smith in 1951 found that in females an average of 2 to 3 per cent of neulroplnl Icukocj'tes have an acce>*sor)' lohide, whereas such ahnormality not present in similar cells of the male, Althongh tins method jcforc any drying ran occur. Immersion in the fixative for 20 to 30 minutes usually suflices, Crc«yl violet or hematoxylin are satis- factory stains. In our laboratory, however, ue u«c the method sug- gested hy Guard,’ in which llic chromatin body is staimxl red and the background green, lire components of the stain being Diagnosis of Intersex Problems 213 Bieljricli’s Scarlel and Fast Green. The following formulations are used by Guard: Biebrich's Scarlet 1.0 grn. Fast Green 0.5 gm. J*ho.s|iholung5tic ncitl 0.3 gin. Pliospbolungstic acid 0.3 gm. Glacial acetic acid 5.0 ml. Pbosphomolybdic acid 0.3 gm. 50/o ethyl alcohol lOO.Oml. Glacial acetic acid 5.0 ml. 50% ethyl alcohol 100-0 nil. Slides are immediately immersed in 95 per cent alcohol for 15 to 20 minutes and then successively passed llirough 70 per cent and 50 per cent alcohol and into the Biebrich’s Scarlet slain, where lliey remain for 2 to 3 minutes and ihcji are rinsed in 50 per cent alcohol. Next they arc placed in the Fast Green stain where tliey remain for a minimum of 2Vi hours. Microscopic control is used to watch for tlic disappearance of the scarlel color from good vesicular nuclei. The length of time the slides remain in the green stain depends upon tlie fresimess of the preparation; in some instances it has been found necessary to leave the slides for as long as 18 hours before satisfactory' results could be obtained. Tlie slides are then passed through increasing strengths of alcohol ijdo acetone, xylol, and balsam, and are mounted. The interpretation of an oral smear preparation (Fig. 2) con- sists of determining out of a 100 suitolde nuclei the number which possess the planoconvex Iiody at the nuclear membrane. In males less tlian 10 per cent of the cells have the body; in females the percentage will lie 30 or over. Barr^ has recently described more than 1 chromatin body within a cell and the number of chromatin bodies as 1 less than the number of X chromosomes. Thus 1 chromatin body — XX, 2 chromatin bodies = XXX, etc. A few words of caution about the chromatin test; First, the lest should he reported as chromatin negatbc or chromatin positive, not as “male” or *'fcma!e”; should some patients liaving a chromatin lest opposed to their sex of rearing or gender role gain knowledge 2t-i ADVANCES IN DIAGNOSTIC UROLOGY figure 2. A pholomicrograph ot an oral smear preparation shewing a number of cells with the planoconvex chromatin hod) at the nuclear merii> branc. Tlie count was ov er dO per cent of the cells liav irig such a body, and the test was reported as chromatin positive. of a poorly worded report, cons^idcrablc wnncco'^soTy' anxiety v\ mtld be generated. Secondly, the chromatin tc»t aids the pliysician in delennining only general areas of interscxuulity; for example, a “lioy*’ vvitli bilaterally uiidc'scendcd testes may he chromatin negative although the possibility of male or true interscxuality has not l)een cstablislicvl. As pointed out in the clas'^ification of intersexes (Table 1), one general claon the interpretation of structures Cvw.’svi avid true eonceming ibc gonads. Here the gross appearance may be deceiving and should never lie rclicvl upon; microscopic examina- tion of properly prepared tissues will give tlic final clue. Fonnalin is a poor fixative for gonadal tissues and a fixative* sucli as Bouiu’s if strongly recommended. Shrinkage and poor cellular Diagnosit of Intersex Problems 245 preservation too often iiinder proper interpretation after formalin is used. ILLUSTKATIVE CASKS Mole /nfcrsexnnliiy Two years prior to consultation, a IS-year-old girl noticed in- creasing enlargement of the clitoris, accompanied hy acne, black facial hair, and deepening of the voice (Fig. 3A). Slie expressed a desire to be like her two normal sisters. Physical examination showed ambiguous genitalia (Fig- 3B) with separate urethral and vaginal ostia. This was confirmed hy endoscopy: in the vaginal vault a small cervix was visualized. Tlie cliromatin test was nega^ live. Excretion of 17-kelosteroids was witliin the normal range and gonadotropins were present in small amounts. A presumptive diagnosis of male iiucrsexualily was made, and an exploratory laparotomy was performed to delennine the nature of the internal genitalia and the gonads (Fig. 3C). A normal-appearing left testis and an ahnormal right gonad, as well as oviducts and a uterus, were found. Tlie right gonad consisted of a gonadohlastoma replacing all gonadal tissue (Fig. 3D), and the left testis was almost entirely replaced hy the same type of neoplasm (Fig. 3E). The uninvolved portion of the testis consisted of seminiferous tuhules containing sustentacular cells with only an occasional germinal cell, and hyperplasic interstitial cells (Fig. 3F). Both ^na.(lltl palient with male ijjlersexuality. (A) Evidence of virilization. (D) Closc-uj> of the external genitaiia showing tiie en* larged phallus and the urethral and vagina! meatuses. (C) The findings at exploratory laparotomy showing the uterus, oviducts, and gonads (the gonads were removed). (D) Photomicrograph of the right gonad showing cords of small, deep-staining cells; interspersed among the cords are larger masses of cells in the center of which appear calcific m3s«es resemfifmg Cafi’-Esner fiorffes. TTie tumor I’lau’ compfetefy repfaced’ Che gonad. (E) Photomicrograph of the left gonad showing testicular tissue on the left and the same t)]ve of neoplasm as found in the right gonad on the right. Only a .«mal! portion of the gonad was not replaced by the tumor. (E) An area of the left testis slwwing numerous seminiferous tubules, for the most part containing only sustcntacular cells, and hyperplasia of the interstitial cells, which was pruhahly the source of the virilizing hormones. Tlie gonadotropin excretion in the urine rose to ca«lrate levels in the \vccks following the surgical procedure. Diagnosis oj Intersex Problems 219 mullerian elements are present, the testes will produce virilization as in the case described above. The necessity for abdominal exploration is evident, and gonadectomy is defmitely indicated in order to control the liomioiial status and eradicate neoplasia. Previous reports of gonadoblasloma have indicated that sucIj neoplasms arose in “female” patients who were actually patients with male intersexuality. Adult Chrotnntin Positive Gonadal Dysgenesis {Klinefelter's Syndrome) Tlte patient shonm in Figure 4 was a 24‘year-old male wlio complained of infertility. Several physical findings, such as lack of Iieard, gynecomastia, and female pubic escutcheon, were noted. The genitalia were normal except for small testes. A semen sample contained no sperm. The assay of 17*kel05teroid excretion was wiUiin normal limits and the excretion of gonadotropins in the urine was at castrate levels. The chromaliti test was positive. Biopsies taken from botli testes presented «imilnr histologic find* inga of hyalinized seminiferous tubules, adenomas of interstitial cells, and occasional tubules containing only siistentacular cells. In other cases occasional tubules contained germinal cells and their presence was compatible with the diagnosis (Fig. 5). It should be pointed out that such le*sticular architecture is not unique for the syndrome, having been observed in amyotrophic lateral sclerosis, true inlersexualily, as well as in other disorders. True Intersexnnliiy A 5-year-old child had previously been seen for ambiguous genitalia consisting of a bifid empty scrotum and hypospadias. A chromatin lest bad been interpreted as negative and, since “testes” could be felt in the inguinal regions, the male sex was assigned. Subsequently the hypospadias was surgically corrected and bilateral orcliiope.xies were later performed. Routine biopsies of the testes were performed and microscopic examination showed 230 A.D VANCES IN DIACNOSTIC UltOLOOV Figure i. A 21*)ear-oKl jialirnl willi KUopfeller'a sjnJriimp, Nole "fur- cop” hairli/ic, g)iicc{imaMia, female |iul>ir escutclipon, small peril*, anil eunuchoid proportions of the hoil}. Cliromalin test «ns iio^ilivc, aixl excretion of urinar) g»rtadotii>]>ins ri»^c to caMTole IcNcU. Tr-ticular l>iop«ies slioned tissue consisting of man) li)a]inized luliules. ndenoinatou* areas of jnter»litta5 cell*, anif an occasional tultule rnnlaining onl) tentacular cells (sec Fig. 5i. Diagnosis of Intersex Problems 233 tliem to be ovolestes (Fig, 6A). Careful examination of tJie sections revealed tlie presence of oocj'tes within seminiferous tubules (Fig. 6B). Tliis case points out the desirability of remov- ing tissue from all exposed gonads, and further illustrates the fallacy of assuming that a patient is a male when the clirojaatin test is negative and externalized gonads arc “testes.” UEFEnENCES !. Barr, M. t.., and Bertram, E. G. A morpliological distinction between neurones ol the male and female, and behavior of the nucleolar satel- lite during accelerated nucleoproiem synthesis, ^alllre, London 103:076, 1919, 2. Barr, M. L., and Carr, D. H. Sex chromatin, sex chromosomes and sex anomalies. Canad. M. 4. /. 83:979, 1900. 3. Bunge, R. G., and Bradbury, J. T. A ten-jear-old boy trith positive sex chromatin test. /. Urol. 78:775, 1957. 4. Bunge, R. G., and Bradbury, J, T. Oocytes in seminiferous tubules: II, A case report of biiacctal ovotestes. /. Clin. Endocrinol. 19:1661, 1959. 5. Bunge, B. G., and Bradimry, J. T. Newer concepts of the Kline- felter sjndrorne. /. Ural. 76:758, 1956, 6. Bums, E. Personal communication, 1900. Figure 6. (A) Photomicrograph of “testicular” tissue from the left gonad biopsied at lime of orchiopexy in a 5-)ear-old, chromatin-negative boy. At the top right is ovarian stroma with oocytes; the bulk of the gonad is com- posed of testicular tissue. The organ is an ovolcslis. (B) Photomicrograph of tissue from the right gonad showing the ovarian and testicular elements and establishing the diagnosis of ovoteslls. At tlie lower left is an oocyte within a seminiferous tubule and at llic upper right is an oocyte within a less well-developed tubule. (From Bunge and Bradbury.'*) 231 ADVANCES IN DIAGNOSTIC UROLOCV 1. Guard, ir. |{. A new technic for (lifTercntial staining of the sex chromatin, and tlie determination of its incidence in cxfo]iale advances in djacnostjc urolocv olfaclory, linpual, ^erlial, and lactHe exchange. Impulses pas'^ing domi ihc spinal cord then excile ihe “erectile center” in the luinho- sacral segment/®’ nliich, of course, may be activated by im- pulses from below, such as arise from a full bladder, from direct stimulation of the external gcnilatia, or from ibc sexually con- gested prostate and seminal xesicles.^® From the spinal cord, im- putes proceed bj way of ibe nervi erigcnles to lumbar and sacral parasympathetic plexuses (mainly S-2 and S-.3) and iulemnl pudendal nerves to the lilood vessels of the penile corpora (pri- marily from the internal pudendal arter>', a branch of llie hypogastric artery). These hnpuKes accomplisli vasodilatation (relaxation of the penile arteriolar musculature) and compression of the dorsal vein of the pcnl-. These physiologic conditions cause tumescence of the peni«, and erection occur?. Achievement of penile erection (tumescence) is an active process induced hy arterial vasotlilatation. Retention of Mood in the cavernous spaces sustains erection and is a passive process. Delumcsccnce, an active process, rc'^ults from vasoconstriction of the penile arteries with stdi'etiiieiil decrease of arterial blood tlow and relo.n«e of llie compre*.«c»l veins.® (The striated muscula- ture of the pelvic floor, specifically the l-chiocnvcrnosu- and hulho- cavernosiis muscles, bring about increase in penile venous pressure by their clonic conlraclion-, which, however, are not esM*Mlial for a sustained erection.) After intromission, the mainlenniice of penile erection depend-* most actively upon loc.il ftirtional-etolic stimvdi to the genitalia (especially llic penis) during stroking coital movements. An “ejaculation center” in the eacral «ml is thought to roach maxima! stiujuJaiion during Jhr hcJghj of .setwaJ rxcitcmeul, JmpuJsr.s from this center to the smooth niusciilatuix* of the seminal vc-iclcs and pro-late re?uli in ojaculalioii, a rapid and forceful sqiicoring of fluid through the narrow ejaculatory diirt*. into the po-lorior urethra, accounting for (hocolatically plea-iirahic scii-aliou. Diagnosis of Sexual Problems in Urology 257 In addition to impulses from the sacral cord, impulses from the thoracolumbar segments may be responsible for penile erection of a mail willi a normal neuraxis. Thus psycJjogenic and reflexogenic mechanisms for penile erection are involved, explaining why pa- tients with cauda equina lesions may have erections, and why occurrence of penile erection may suggest the existence of an in- complete lower motor neuron lesion. Reflexogenic erections were observed by Bors and Comarr® in a high percentage of complete upper motor neuron lesions at any level, but with maximal inci- dence in patients willi cervical lesions. Such observations indicate tliat the length of the caudal stump of the spinal cord is important for the autonomic reflex function of erection.® Ejaculation and orgasm are interposed between tumescence and dctumcscence. Ejaculation is subdivided into seminal emission and true ejaculation. Seminal emission incorporates the contractions of the smooth muscles of the bladder neck, seminal vesicles, prostate, and vasa defcrentia. Ejaculation consists of clonic contractions of the hulbocavernosus and iscliiocavcniosus muscles and associated movements of the other striated muscles of the pelvic floor, lower extremities, and trunk. Ejaculation involves complex reflex mechanisms and is liigiily vulnerable in spinal cord injuries; it may remain absent despite otherwise adequate se.xual per- formance.® Orgasm is a sensation said lo be caused by contraction of the smooth muscles of the internal se.xual organs, pieccding and aho coinciding with seminal emission and ejaculation. Orgasm fades in tlic fonn of a voluptuous languor of tlie postcoital moments. From this brief description, it is apparent that multiple co- ordinations of psycltic and physical forces are necessary lo initiate and complete precoital and coital activities. Tims at many sites and in many phases a man’s sexual performance may be disturbed. 25« ADVANCES IN DIAGNOSTIC UROLOGY rh)iicnl Maturity The present coiiMncnts on sexual potency are limited to en* docrinologically and ph>'sically nuitufc males aWiIi previous sexual experience. Exact age of physical maturity is intcnlionally not delineated here, since many adoIe’«cent hoys may he, as Kinsey and colleagues'^ have pointed out, far more knowlcdgcahle, expe- rienced, and sexually active lliaii their chronologic seniors, ily excluding an investigation of the preadolcscenl youth, ue avoid lengtlvy digressinns into p^jchologic mechanisms of extreme com- plexity, which are generally incompletely understood and often subject to dispute among psychiatrists.'® Knrly SexunI Kxperience Masturbation, although a universally common form of erotic outlet in early sexual awareness'* is nonetheless socially dis- approved for vague and inaccurate reasons. Thus guilt feelings are provoked liy ni.i>turhation, and lingering fears of self-inflicted damage may seriously affect later heterosexual patlcni und per- formance. Similarly, premarital coital experiences inlluencc later responses, even us to the physictl oppearante of the partner and mode of copululory intetplay.’® From these origins various deficiencies in sexual ability, .such as failure to acquire erection, premature or absent ejaculation, and jnahility to engage in iiilcr- course on later occasions arc encountered without organic dis- ease.*’* For example, so-called “specific (selective, situational) genital impotence,” difficulty in cohahiling vvith a specific per.son, is of psychologic origin. Psychotherapy is helpful in many such instances.** Parental or religious education may inculcate in a child the uolioii that sox is “dirty oml indecent.^’ Suhcou'-cious reactions again«‘l coitu-' can thus result and lead to various Ilmilalioas of potency; for example, a luilicnt may suffer specific genital linpo- teiu’c V'itli his wife, hut may lie able to perform with a “low-.scale woman” such as a proslilute.** Diagnosii of Sexual Problems in Urology 259 Ancient proliibitions against sexual intercourse were devised from superstition. Indictments against coition during menstruation so originated; they Ijave been reinforced througlmut the centuries by implications that violation would make the man sick, or, if the woman conceived, tyould produce a feeble or insane cl)ild.® The impact of the subconsciously accepted superstition will be self* evident. In a few words, the sexual exploits of young hoys comprise the experience upon which their later physical and emotional sexual patterns are formulated. Liberally intermingled are ill-defined social taboos, parental abstention from discussion of sexual matters, or fragmentary “guidance” from various (usually illicit) sources — all culminating in the individual’s acquired sexual behavior. I'arieiies of Impotence Numerous classifications of impotence Imve ))een proffered.’’ 18 . 10 . 45 Some specify impotence as complete, partial, temporary, or permanent. Olliers distinguish, in varying detail, the phases of Sexual incompetence, such as inability to acquire erection, In* ability to achieve penile insertion, premature ejaculation, and failure to ejaculate. Such detail may be Irouhlcbome and without practical value. In essence, potency is of either organic or psychogenic origin. The latter is exclusively or predominantly causative in over 90 per cent of patients.^’’ Hastings’ categories of organic causes^’ include (1) systemic disease, (2) disease of nerve or blood supply, and (3) local disease of the genitourinary tract. His summary of psychologic causes, as appHcahle to the mature male, is simply “inhibition of normal potency”* • This chaptfr sfwoificallf ©mils »ho#e groups clieJ hy llasling* under “jnlijbjtlon ol normal poicney In the sejually immalwe’' and under “neurotic impolenfe,” i e., ihoie groups manifesting defects in psychologic desclopment.’" 260 AD\’ANCES IN DIAGNOSTIC UKOLOCY Organic Causes oj Jmpotenee General groups and siiccific disease entUics arc aggregated for our present purpo«cs as foHows: 1. Systemic illness. Any acutely or clironically cne^^•at5ng di'ease diminishes or impairs libido and potency. The fnndnmetital drives Io^\ard suni\al and rcciiperalion laVc precedence over seviial HCli\ii}es. It is not true that diseases such as luherculosi-< enhance sexual appetite.''* It is inic that clironic alcoholism and drug addiction do reduce sexual activity,'* although the personality problems that lead to such dependency on alcohol and drugs are obviously important. Cachectic proce''ses veaken the patient and depress his sexual interests. Impotence is more common in diabetics than itt chronologic contemporaries. It is occasionally reversible {but not always jicnnancntly) with control of the disease.**'^® In the Leriche. syndrome thrombotic occlusion of terminal aorta occurs. The complaint prc'eiitcd by the>c patients may lie inability to maintain penile erection. Lumbar .«)inp.tlhcclomy or tliromlio- endarterectomy often accomplishes c.irly return of potency.** 2. Dlsennes of nerve or blood eiip{>Iy. Any progressive disea'c of the central nervous system, such as tei1i.ary syphilis, multiple sclerosis, or other iliiTiisc involvements of brain or «pinal cord can rcvull in sexual impotence, but none invariably precludes potency. Trauma of the spinal cord can produce impotence, reversible to varying degrees during the nionllis of recovery.* * Temporary sexual impotence may result from reversible neurogenic bladder; llie correct cvaliiaiion of the Impotence nuy lead to an important diagnosis of vesical malfunction.** Specific interference uith the blood supply to the penis, such as onnirs in the I-crichc syn- drome (see above umler Systemic Illness), may alTcct sexual potency. 3. rondttions of tlie BcnJunmnnrj' tmet. A numl>er of local conditions of the peni< v.w afTcvl ptAcncy. In Peyronie's disease, or plastic induration of the jjcnile corpora, erection is pain- ful I>ccau‘e of penile curvature. Ilccausc intercourse is too painful. Diagnosis of Sexual Problems in Urology 261 the patient abstains. NonspeciBc chordee may be superimposed, in advancing age, upon mild, unrecognized congenital defect without hypospadias. Venereal or tieoplaslic penile lesions^ can cause local pain and deformity of the glans penis and produce painful erection and intromission. Priapism, or protracted, nonerolic penile erec- tion, can cause rupture of the vascular lacunae of the penile coipora %yitli subsequent fibrosis and prohibition of penile engorgement.® The size of the penis can be a source of difficulty in that undue self- criticism and shame regarding a small penis may cause some forms of impotence.^® Penile size bears no relationship to the degree of sexual satisfaction of either partner: patients with a large penis may suffer all the forms of impotence.®* There may he mechanical impediments to coitus, such as a large liydrocele, an inguinal Ijernia (especially with scrotal component), or scrotal elepliantiasis,*^ Local trauma to the penis, such as accidental “fracture of erect penis,*’ self-inflicted trauma (m efforts to break chordee), or psychotic self-mutilation, is a hazard to potency. Trauma may also occur to the perineal nerves, such as may follow extensive and severe straddle injury, witli or without fracture of the ischiopuhic bones. Surgical trauma can occur in several forms. In subtotal penile amputation, usually performed because of malignancy, impotence is not common wlien tlie patient is encouraged and reassured. Castration produces impotence wlien it is performed in the pre- pubertal boy having no previous sexual experience. Potency may remain intact after traumatic orchiectomy in the se.xually experi- enced patient, or after castration of an adult for carcinoma of the prostate (though often depressed by estrogen therapy). In lumbar sympatliecfomy for peripheral vascular disease, potency is usually preserved (though perhaps impaired) unless ganglia arc removed bilaterally below T-12. After abdominoperineal resection, damage to the lumbar sympathetic system is greater in excision of rectal cancer®* and less in ablation for ulcerative colitis,®'^* but impo- 262 ADVANCES IN DIAftNOSTJC UnOLOCV lence not an irivariaWe result.^' After radical prosla* iDclomy, impotence may occur (b«l not invariahly).’"' 4. General, Bfqwired contlition«. Disfiguring disease or cos* metic defonnilies such as facial hums, generalized psoriasis, or other repuUivc ailments may play a role in impotence. Wlicn the patient and his prospective coital partner arc emotionally dis- tressed, impotence may follow. Tlie patient with a canliovascular disalality may be fc.irful of aggravating existing liearl disease or of causing fatal damage to the heart. E\en minor conditions such as u small inguinal Iiernin may cause the patient to abstain in fear of “exertion of coitus.”"' Tlic l>a«is for impotence in llier>e and similar condition-* is psy- chogenic, often recognized and accepted as Mich by the patient. Depressed li\cr function can affect potency. After severe mab nutrition or certuin hepatic parenchymal diseases, the damaged liver is thought to catabolizc lc«s efficiently tlie circulating estrogens nomwlly present in the male.' Tlie altered cslrogei^aiulrogen equilibrium and con'equciil high tiler of female iiomioncs could depress sexual potency. Our present inability to measure endocrine metaboUles limits our knowledge of ibc^e occurrences. Moreover, severe illness or sturvatiou depresses libido, since su^^■ival takes precedence over reproductive activities, Admim«lcring vitamin H complex .Tiid improving nutrition may rcver?e the impotence. Smerc generalized arthritis can enuM: assumption of the coital position to be so difficult or coital nio\cmcntsso painful iliat capula- tion is not attempted. The psjxliologic impact of extensive bodily lr.ninia can Ik; damaging to potency. Even after mechanical impediments to coitus /nllouJwg Major and fiarrr hod} traun/a hci-n oiorromo, the p.iticnt may docloji a conviction that impotence is inevitable after so «erious an injury. Venereal complications may l»e diverse. Apart from central nervous sy?tem lues, a j>atienl with, for example, urethral stricture Diagnosis of Sexual Problems in Vrolo^ 263 and urinary infection may fear, ignorantly and incorrectly, that coitus will aggravate the venereal complications or will impair gen- eral health, whicli, in tunr, will aggravate the venereal complica- tions (psychologic sequel to existing organic disease). Alcoholic or narcotic addiction may later affect potency. Un- inhibited sexual license may occur in the early pljases of addiction, while the patient is under the influence of drugs. Later, as ha!)itua- lion becomes ingrained, organic impotence prevails, coupled with psychophysiologic preference for drugs rather than for sexual activity. Barbiturates taken in large doses or for long periods of time are known to produce “chemical impotence.” The effect of tranquilizers lias not yet been objectively studied, but tliey may exert cognate effect.^’' As Hastings indicates, the combination of business pres- sure and the use of tranquilizers and alcohol during the day and barbiturates at Iicdtime may well lead to sexual impotence on iioth emotional and cliemical bases. In general, decline in libido and potency occurs with advancing jjgg 18,21,30.45 jjj preclude potency in many Individuals*,^® social and psychogenic factors also play a role. Some aging men forthrightly elect to abstain from coitus, either in deference to the “dignified companionship” they believe is expected of them or “to conserve energy” for a preferred avocation.*® Such men may be impotent with their wives, although they are physio- logically potent. Psychogenic causes of impotence, then, may lie superficial or deep, transient or possibly permanent. A listing of such causes, or even a classification of groups of causes, would be pointless in that the individual problem is not elucidated tliereby. Dissertations upon tile major causes and their ramifications have been published.*®' 21.32 yijg perspicacity of the first pJiysician who sees the patient w'ill enable him to determine the severity of tlie psychogenic im- potence. The physician must then either undertake treatment him- 261 ADVANCES IN DIAGNOSTIC UROLOGY self or advise tlie patient alioul any 5[»ccialized aid warranted by his particular prohleni. If the atlemling physician can do the patient no good, he inu'^t at least abstain from making Inin worse (through ignorance or ineptitude). It is imperative to avoid the c\er*presenl danger of fixing the existence of a problem in the patient’s head, 5. Iatrogenic influences. Whether the plij-sician is s)mipntliclic and attentive or cold and indifferent profoundly influences the sexual performance of the inquiring patient, young or old. Tlui«, for example, the physician’s adtice may dissuade the cardiac pa- tient from sexual activity, when merely a change in coital position (the wife .assuming the on-top position)'** would permit him to ha\e intercourse witli safely. Implied or overt di«couMgement hy the urologist may prechulc a patient’s attempt-* at intercourse after prostatectomy. No surgical route of prostatectomy consistently re- sults in prosersalion orlops of potency,’* hut c\cn a nicnllou of the possibility of po-toperativc impotence may initiate impotcncy.®’ I oppose adsising tlic patient m ads'ance of operation of the pos- sibility of impotence after prostatectomy, preferring to answer his inqulrj- with the casual remark, “It will lie aliout the same/’’* Ollier urologists, howe\cr, urge that the paticut he informed of this potential loss.® U R O I. O G I C n I A G N O S I .S O T .SEXUAL Ml I* O T E N C E Winning Confidenrf During intiinatp Ilitlory The urologist occupies a unique position for cstahli«luiig a diagnosis of many psychoscxmil prohleins and rendering ap- propriate therapy. U a palienl eomes dirvelly to die urologist, he does «o on the premise that a Iiighly iraiiicd iiidi\ idual will rapidly identify and soUe the problem. If a patient is referred to the urologist, the referring physician has usually paved the way for a cooj>erati\e relationship wherein intimate matters are divulged, in Dizaah of PrcfS^i £= Crc^ ;63 coElnsl kbJ) tie nSioKite 2 pj!i=i; crir ' ^- phTsician. »Ao raiT ® ™,'„ the ihe first fnnctiott of the Wogo-t is ^ cpnfideoee nhich the petienl is prepi^ the I baclache, peiir.eel dLW.«- -d lasstPtde paliBH’s basic piobleni bro..„ht as .uch bv "o7.',':.".„ b. ... .b.. . elfectiTe historian. He must 1 * alert to U.e e Euspeded diabetes mellitus- He inu=t ^ intemiittenl of Lriche’s Si-ndrome and ini^fiple „„5b claudication by seeking dinunis f™ ,1 5 i(,„er aWominal systolic munnur is frequendy " examinaUon quadrants and femoral ^7^ aclrt-Tbs:- of superficial is ueU within the scope of "■' “ 7 ' ,„ai lead to alidominal and cremasteno re . -. ,0 jasulting from identification of a revers.ble „ „rious forms is recent, severe, generalized Uauma. Impotence commonly associated iritl, neurogenic bladder. Kertroi-n. fn V.e of j „,ainst pressing too An important precaution j" ^ ®„.,n„„e„talion. In many cntliusiastically for urologic lagn . -...aboeenic basis must be patients who complain of impotence, ^ppro. recognized in its own right, y- . 1 wc hTD0-paili*8 unJeseeniletJ •Urologic dbgncU of congonl.al a«. testicles) which could later gne me to ^ consensus i^ong for the most part, rather *‘«»eh»fom.rd. « cnl. and OAer-ail surgical lech- witl. regard to therapeutic ntque concerning corteclible coogeni«»i problems. 266 ADVANCES IN DIAGNOSTIC UKOLOCY prialely ^^hile the patient's response to encouragemenl and to suggestion of simple precoital and coital techniques is analy7ed. Cystoscopic examination may sen’e only to Tlx Uie con- cept of organic disorder in the minds of many sensitive and intro- spective patients (especially if they liavc been to many doctors wilb tlieir problem). TJiey will then lielieve that the urologist Jias over- looked the site or nature of the true cause of iJieir impotence. Some patients subconsciously seek the discomfort associated nidi cys- toscopy as a form of self-punishment or castration.^'*’ Cystoscopy does have a useful place in selected instances. Prostatitis, for example, may pro\c to be the c sexual bunglings are common and will automatically disappear with experience. Urologic problems, sucli os “honeymoon c>‘stiti5” (secondary to vigorous coital activity) with or wilhonl bacterial involiemcnl, may beset the newly married girl. Trichomona) vaginitis may be di*'COt cred after the organisms are found in the husband's prostatic secretion. Cotrelnlions of degree rather than kind can be made, for the most part, between the sexual problems of tlic male, as detailed in the first section of this chapter, and tho-e of the female, now pre- sented in cursor)' fashion. Lengthy commentaries on sexual heliavior of the female are availahlc clsewlicre.'** It is .sufiicient to note here that an altentiie physiriaii who can win his patienfs confideiire, who c.m suppress his own prejudices in the hearing of his patient's inliiualc reielations and w)m is alert to organic and p-iyehogrnic entities will rcmler most suitable aid. In dealing ssith so compelling » force in human actiiity as sexual drive, the phjsiciaii mu-il exploit fully all his personal tesourex's in hchalf of the profound conlriliulioii that he may offer to hi« pa- tirnt’s immediate and long-term welfare. Diagnosis of Sexual Problems in Vrology 269 REFERENCES 1. Biskind, G. B., and Biskind, M. S. The nutritional aspects of certain endocrine disturbances. Am. J. Clin. Path. 16;737, 1946. 2. Bors, E. Neurogenic bladder. Vrol. Surv. 7:177, 1957. 3. Bors, E., and Comarr, A. E. Neurological disturbances of sexual function with special reference to 529 patients with spinal cord injur). Vrol. Surv. 10:191, 1960. 4. Calloinon, F., and Wilson, J. F. The nonvenereal diseases of the genitals: Etiology, differential diagnosis and therapy. Springfield, III. : Charles C Tliomas, 1956. 5. Dahlen, C. P., and Goodwin, W. EL Sexual potency after perineal biopsy. J. Vrol. 77:660, 1957. 6. Donovan, M. J., and O’Hara, EL T. Sexual function following sur- gery for ulcerative colitis. New England J. Med. 202:719, 1960. 7. Eller, E. A. Hypogonadal impotence in middle-aged men. Arizona Med. 17:217, 1900, 8. Evans, B. The natural history of nonsense. New York: Knopf, 1937. 9. Fjnkle, A. L "Paraphimosis, phimosis, priapism.” In Conn, H. F. (ed.), Current therapy. Philadelphia and London: Saunders, 1961. 10. Finkle, A. L. Sexual potency and the physician. Afetl. Times 88; 557, 1960. 11. Finkle, A. L. Surgical repair of denuded penis and scrotum. South. M. J. 40:1092, 1953. 12. Finkle, A. L., and Moyers, T. G. Sexual potency in aging males: IV. Status of private patients before and after prostatectomy. ]. Vrol. a4;152. 1960. 13. Finkle, A. L., and Moyers, T. G. Sexual potency in aging males: V. Coital ability following open perineal proslalic biopsy. /. Vrol. 84:649, 1960. 14. Finkle, A. L., and Saunders, J. B. deC. M. Sexual potency in aging males: 111. Technic of avoiding nerve injury in iierineal prostalic operations. Am. J. Surg. 99:23, 1960. 270 ADVANCES IN DIAGNOSTIC OnOLOCY 15. Finlde, A. L, Mo)ers, T. G., Tobcnkin, M. I., and Karg, S. J. Sexual potency in aging males: L Frcriuencj of coitus among clinic paUenls. J.AM.A. 170:1391, 1959. 16. Gliosh, S. Management of scvtial debility in joung men — the abu»c of testicular hormone. /. Indiana M. A. 3I:1&1, 1958. 17. Hastings, D. \V. Ps}clioIogic impotence. Postgrad. Med. 27:129, i960. 18. lluhner, M. The diagnosis and treatment of sexual disorders in the male and female. Philadelphia: Davis, 3939. 19. Kaplan, A. II., and Abrams, M. Ejaculatory impotence. J. Urol. 79:961, 19.70. 20. Kaufman, J. J., and Borgeson, G. Man and se.x. ^'ew• York: Simon and Schuster, 1961. 21. Kinsey, A. C., Pomeroy, W. B., and Marlin, C. L Sexual behaiior in the human male. Philadelphia and London: Saunders, 1918. 22. Kinsey, A. C., Pomeroy, TT. B., Martin, C. £., and CeLhard, P. H. Sexual behavior in the human female. Phil.iilcljdiia and London: Saunders, 1953. 23. Kroger, W. S. Psychosomalic aspects of frigidity and impotence. Internal. Rec. of Med. 171:169, 1958. 21. Leader, J. A. Ciironic tc»ieulopro«Iatitis: A rcorieniatinn. J.AAI.A. 168:99.5, 1958. 23. Mead, M. From the south seas. iVeu York: .Morrow, 1939. 26. Menniiiger, K. A. Psychological factors in urological di9f3»c. I'sychoanaljl. Quart. 5:188, 1936. 27. Mcnningcr, K. A. Some obseoattons on llie psychological factors in urination and gcnilO'Uriiiary afllktions. Psyehoanaljt. Rev. 28: 117, 1911. 28. Meyer, B. C, and Lyons, A. S. Kctial rcH'Clioit: Paycbialric and medical management of its sequelae: Ilcport of a Psyehosnm. Med. 19:152. 1957. 29. Morgan, J. W., and Saunders, J. B. deC M. I’resenation of genito- urinary function in rectal resection. Proc, Roy. Soc. Med. *13:1081, 1950. Diagnosis of Sexual Problems in Urology 271 30. Newman, G., and Nichols, C. R. Sexual activities and attitudes in older persons. J.A.M.A, 173:33, 1960> 31. O’Conor, V. J., Jr. Impotence and the Lcriche syndrome: An early diagnostic sign; consideration of the mechanism; relief by endarter- ectomy. /. Urol. 80:193, 1958. 32. Oliven, J. F. Sexual hygiene and pathology. Philadelphia and Montreal: Lippincott, 1955. 33. Rubin, A., and Babhott, D. Impotence and diabetes mellitus. J.AM.A. 108:498, 195a 31. Sandler, J. Tlie body as a phallus: A patient's fear of erection. Inlernat, ], Psycho-Analysis 40:191, 1959. 35. Sfix function after rectal excision. “Annotations,” Lancet 1:189, 1959. 36. Shev, E. E., and Finkle, A. L. Reversible neurogenic bladder fol- lowing cerebral and/or spinal cord concussion. /. Urol. 81:653, 1959. 37. Silagy, J. M. Personal communication, 1962. 38. Silagy, J. M. “Psychiatric aspects of diseases of the genito-urinary system,” In Dcllak, L. fed,). Psychology of physical /7/new. New York: Grune & Stratton, 1952. 39. Smith, D. R. Estimation of the amount of residual urine by means of the phenolsulfonphthalein test. /. Urol. 83:188, 1960. 40. Smith, D. R. General urology. Los AIlos: Lange Medical Publica- tions, 1961. 41. Stahlgren, L. H., and Ferguson, L. K. Influence on sexual function of abdominoperineal resection for ulceratite colitis. New England J. Med. 259:873, 1958. 42. Tushnet, L. Impotence and diabetes mellitus. /. M, Soc. Netv Jersey 57:256, 1960. ‘13. Van deVelde, T. II. Ideal marriage: Its physiology and technique. New York: Random House, 1957. 41. Wellman, M. Specific impote/ice in the married njale. Canad. Psych. Assoc. J. 3:87, 1958. 45. Wersbub, L. P. Sexual impotence in the male. Springfield, lib: Cliarles C Tliomas, 1959. APPENDIX I. OUTLINE or history and PHYSICAL EXAMINATION IN NEUROLOGIC UROLOGY* Name; Ace: Hospital Number; IlfSTORY SUMMARY: A. Neurologic Coniultation Diagnosis: B. Psychiatric Consultation Diagnosis: C. Tentative Final Neurologic Urology Diagnosis: D. Recommended Management: E. Name of Patient’s Home Nurse: F. Name of PatienCs Social JForker: Date: • Preparnl bj Ernest Bor* and Haderkk D. Turner; in use io the Deperljnent of Surgrry/Urology, University of California Medical Center, Los Angele*. 273 274 AppcndiK I BLOOD I’RESSLTiE (Autonomic dysreflexia If lesion abo\e T4 j) a. Date and B.P. — b. I'ersp'iring or flushing of lace — c. Bradycardia— d. Ilcadaclies — c. Goose pimples, chills — f. Paroxysmal }i)'perlen$ion — ]. Past justoky (in detail) 1. Childhood. Adolescence. Adult «levelopmcnt. 2. Mcnarche: ogc of on«ct, number of days, cycle, degree of flow. 3. History of diabetes. Family liislory of diabetes. d. History of boue) habits: frc(|ucncy, regularity, consistency. S. Past di«cacho!ogic inconlincnce after lotolomj (docjn’l care to con- tain tnicturilion under soctatl) unacceptable conditions), 3. Stress incontinence (L.M.N.L.). 4. OierJlon incontinence tU.M.N,L. or L.M.N.L.; complete or incomplete). 5. Keflex incontinence (spinal coni injur)): U.M.N.L (5)no* n)ms: normal cord bladder, automatic bladder, neurogenic reflex bladder.) 6. Incontinence ot nonresislatice: '^dribbling" (combination of botli U.M N.L. and c.g., spina bifida). IV. Bowel iitsTORv 1. Frequenc); Jail) or r%er) 2 or 3 da)8? 2. Desire to deforale? If present, llie lesion is incomplete. 3. nifterentialion of pss or fecal mallei? If pres-ent, an intact autonomic nerxe *uppU to rectum is indicaterl. 4. Sensation of fecal matter passing the anal ranal (associated ixr- ceplion of touch, jiroprioception, and lemperalurc in anoculane- ous junction)? Appendix / 277 5. Initiation? DifTicultj' in initiation is not specific for U.M.N.L. or L.M.NX. G. Interruption (in presence of diarrhea) ? Incontinence is not specific for U.M.NX. or L.M.NX. V. Sexual HtsTORY Male: 1. Erection. a. Complete U.M.N.L. has reflex erections. h. Incomplete U.M.NX. has psycliogenic or reflex erections. c. XM.N.L (complete or incomplete) may have psychogenic erections. 2. Ejaculation? Usually absent in complete U.M.N.L.; absent in patients with complete L.M.NX. without erections, a. Emission? Rare in patients with U.M.N.L.; not infrequent in patients with l^l.N.L. and erections, h. Keflex contraction of hulbocavemosus and ischioca\er- nosus muscles? Rare in patients with U.M.N.L; does not occur in L.M.N.L. c. Orgasm? Lost in patients with complete U.M.N.L; may occur with L.M.NX. Female: 1. Dyspareunia? Not present with complete interruption of spinal cord pathways; presence indicates conduction by respective pathways. 2. Frigidity? Usually psychogenic. Jpperulit I 3. Lack o{ orgasm? Usuallj psjcUogcnic. VI. UnOLOCIC rROCEDURES 1. Ice water test; 2 ounces of sterile ice water is injected Into the empty bladder by means of a 16 French whisllc-lip callicicr. Record the exact \olumc Mhtcli is or is not expelled, and the potentially retained \oIume, within 60 seconds. If fluid is not expelled, record whether or not the catlicter was ex]>el]etl. In patients with U.M.N.L it w expelled except in spinal shock. There is tio tesponse with I*M.N.L. or i\orinal btaddei. 2. Cyslomelcj and sphincterometry: dales and interpretation. 3. Retrograde cy stourcthrogram (A.R. and lateral and A.R. 30' rain, delayed cjslogram): dale and diagnosis. Is there tC’-ieo- ureteral redux? I)e«cription of contour and sire of bladder. 4. Voiding cystourethrngram (if {mtirnt can void). a. A.P. roentgenogram. Is there xesicouretcrnl reflux? lluring xoiding only? b. Fluoroscopy, when imlicaled, xtilh urologivt present. IJfscription. c. Cineradiography (when for reyicalcd ob«er\alion it is de- siraldc to rerun a rdin of nitclurilion). 5. IliiTcrcntial uroflomelry (iwvxidetl the patient has the desire and ability to start xulitional micturilinn), a. Voided tolume In cubic centimeters per secojid during spontaneous niiclutition without catheter into the Uroflo* tnetcr. Appendix I 279 b. Voided volume in cubic cenlimeters per second through an indwelling catheter into Uroflometer after retrograde instillation with normal saline. c. Is there a difference between a and b? In the absence of bladder neck obstruction, the curves a and b will be similar. 6. Intravenous urography (to he done once a )ear in patients with bladder balance, or more often if indicated). Note anj anomaly of bony spine observed on K.U.B. 7. Test of capacity and residuum (if any) 1 hour after removal of catheter. Residuum/capacity ** 0 per cent in patients with perfect bah ance; 20 per cent for U.M.N.L. and 10 per cent for L.M.N.L. are permissible. 8. Cystoscopy and bladder mucosal sensory perception studies; Lateralization. Absent in lesions above T*12 segment. In lesions below T*12, dome, side walls, and orifices may perceive stimula- tion, but the trigone does not. Description and significance of responses: a. Dome: lhoracolural»ar innervation. b. Fundus: thoracolumbar innervation. c. Trigone; sacral and thoracolumbar innervation. d. Lateral ivalU: thoracolumbar innervation. e. Ureteral orifices: thoracolumbar innervation. 9. Laboratory data: urinalysis and culture, B.U.N.> creatinine, C.B.C., l-hour total P.S.P. urinary excretion at 15-minule intervals. 10. For U.M.N.L., topical Ponlocaine anesthesia of the vesical mucosa. Determine ratio of capacity to residuum before and 280 flppenifiK I 1 hour after inslUlation of 60 to 90 cubic centimeters of O.l to 0.25 per cent aqueous Pontocaine wilulion tlirough vihi«.tl«s tip catheter for 10 minutes. Remove Pantocaine before catheter removal. Test residual urine again after 2 1 hours. 11. Puiiernial nerve aneslhis^ia. a. Dates; b. Ucsiduunr^capacitj before and after, in per cent: c. Was there improvement in ease of voiding? 12. Dilfcrential sacral nene anesthesia. a. Dates: b. Residuum/capaeil) Wfore ami after. In per cent: c. Was there improvement in ease of voiding? ]5. Comhined anesllicsla. a. Topical vesical mucosal onesthesia with 60 to 90 cubic centimeters of a 0.1 {ter cent aqueous Pontocainc solution combined with pudendal nerve Mock: iraiduuni/ropaclt) l>efore and after, in per rent. b. Pantocaine comhined nitli sacral nerve nnrslhrsin; re- siduum /capacit) Wfore and after, in per cent. VII. NKi’nouM,ir KXAvrisvTioN 1. Urologicall) signinrani reflex artivitp. a. External rnial sphincter. Tone and volitional funriion of contraction and relaxation also indicate function of the ex- ternal urethral sphincter l»reause of the same nerve suppb ( 53 - 5 ). Appendix I 201 b. Anal reflet stimulus of pin prick in S-5; visible sphincter conlraction. c. Bulbocavernosus reflet (1^-5 — S-5). Squeeze llie glans penis gently or tap the clitoris gently and digitally test rectally the anal sphincter response. Is rectal sphincter contraction normal, absent, or hyperactive? If there is an indwelling Foley catheter, give a gentle tug on the catheter with an index finger in the rectum. Let patient cough and test the response. 2. Other reflex activity, pathologic finger aneii!oi^c!c co>5ultatiox svmmabt Untlcr this heading is recorded a brief s)nopsi9 of evicntial findings and llie neurologic diagnosK together ssitJj tlie consultant’s name for fuTthcT reference or rntjuiry. B. The rsvcuiiTnic consuetatiov Tlie psychiatric consultation, when indicainl, should l>c brief and should include the pertinent facts ond diagnosis. C. Tttc tentative nsAL diagnosis The tentative final diagnosis indicates the type of neurogenic bladder, i.e., upper or lov»cr sertsory-motor neuron !c«ion, complete or incom- plete (e.g., spinal cord injury), exclusive sensory neuron lesion (eg- tabes), nr exclusive motor neuron lesion (e.g., poliomyelitis). D. The becommended iivNvcEviEsr The recommended management should indicate procedures rontem- plated for live future, as listed elscvvhere.* * Hors, Comirr, A. and Moulton. 5. H. Tlie role ol nrrve MorLi in the nvanaxenveni tri Inumatie enrti bladders*. Spiast titrttlirsia, aabaraebnoiil alcohol in- Jecllona, pudetiilal nerve anepcrten«ion, 92 selerti\e renal aTteringrapliN, 17 techniques, R-22 Iransaxillary, 11-16 Iransfemotal, leuoprade, 11-1 1 Iranslumhar. 0-10, 76 Arfonad, u«e of, 27 Arteriogram. See Aortogtaph) Atherosclerosis and li)'pcr1ension, 77, 00 of renal artery, 3 Atrophy adrenal, nith tumor, 162 of Lidney, photovanning of, 190 Rcnrodioianc test, in pheochromo- cjloma, 178 Riopsy percutaneous needle, of Vidnry, 110-135 adequacy of, 12.3-125 complications of, 125-133 contraindications 113-11,5 death* from, 125-126 for iliapnosi*, U1-U2 equipment for, 116 hemorrhage from, 120-129 indications for, 111-113 infections from, 131 Itersen-Roholm technique, 117 Kark-Muehreke-Pirani lech- riique, 117-122 kidney function after, 132- 133 ojieratise inler'ention in, 12<^^- 120 pain from, 1.31 postoperathe routine, 122-123 preoperatise routine, 113 teerceplinn «luii»es, 219- 219, 278 neck ohMrurtion cyilopraphy In, 41-12 cystourellirograjihy in, 63 Index 287 neurogenic djsfunclion, 203-233. See abo Neurologic urology Blood supply, renal arterial, 4-7 Bonnevie-Ullricli syndrome, 236, 240 Bowel history, in neurologic urolo- gy, 210,275-276 British anti-le^visite, with chlorme- rodrin, 193 Camera, cystoscopic, 224-227 Capacity/residuum ratio, bladder, 217, 278 Carcinoma adrenal in Cushing’s syndrome, 166 hormonal diagnosis ol, 149- 154, 169 radiography in, 154-164, 171 treatment of, 168 in virilism, 171 prostatic, 136-146 cytologic study of prostatic fluid, 141 disseminated, 142-144 estrogens affecting, 142 open perineal biopsy in, 141- 142 perineal needle biopsy in, 137- 139 serum enzyme determinations in, 140, 142 Iransrecla! needle biopsy in, 139-140 transurethral prostatectomy in, 140 Carrot sign, 63 Catecholamines, urinary, in pUeo- chromocyloma, 177 Catheters, history of use of, 208, 274 Children antegrade pyelography in, 47 biopsy in, 115 cystography in, delayed, 33, 35, 36, 37, 39 cystourethrography in, 63 transiumbar aortography in, 10 Ciiiormerodtin BAL with, 193 labeled with mercury, 193 Chromatin, and intersexuaVily, 232, 236, 237-238 Chromatin lest, 242-244 Chromosomal sex, 233 Chromosomes, and intersexuality, 232 Cinecystophotography, 229-231 Cineradiography, 214, 277 Circulation, paracaval collateral, 55 Corticoids, excessive release of. See Cushing’s syndrome Cortisone, effects on 17-kelosieroid excretion, 170 Creatinine concentration, in hyper- tension, renovascular, 95 Cushing’s syndrome, 147-168 adrenal atrophy in, 162 diagnosis and localization of, 166 hormonal differentiation of, 149- ISl and obesity, 149 radiography in, 154—164 sella turcica in, 163, 165 spironolactone test in, 175 treatment of, 161—168 Cyst of kidney, photoscanning of, 197 Indtx 2 }{« C) st — Continutd pancreatic, radiograph) of, 161 C>stograph) in l)Ia(l(!tr neck oli0 in intrr««kualll), 210-21! C)«louret}irugraph), 02-67 choke, 61 retrograde. 63, 211, 277 > aiding, 63. 21 1, 277 Defecation, hi276 Genetic sex, 233 Getiilalia, in lnter»exuality, 233- 231,236 Cerota’s fa*cia, identification of, 157, 100 Glomerular rihrotinn rale, in h)jirr- tension, rcno>n«eular, 92 Gonadal set, 233, 237 Gonads aplasia, 2.35 slysgenesis, 233 inu«lraiixr case, 219 in inlersexualil)', 230 lleiiiatomn, after Idop*), 129 Index 2R9 Hematuria after biopsy, 127, 128 biopsy in, 112 Hemorrhage, after biopsy, 128-129 Hermaphroditism, male, 234 Hippuran, radioiodinated, 184, 192 Histadyleucine, 76 Histamine test, in pheochromocy- toma, 177 History-taking, in neurologic urolo- gy, 205-213, 272-277 Howard test, in renovascular hyper- tension, 9S-91 Hy drocorlisone hyTiersecretion, 147-168 See alto Cushing’s syndrome Hydronephrosis angiography in, 3 pyelography in, antegrade, 44- 53 17‘Hydroxycorticoid excretion in adrenal adenoma, 151 in adrenal carcinoma, 151 in adrenal hyperplasia, 151 in Cushing’s syndrome, 149 in obesity, 149 Hypaque, use of, 22 Hyperplasia adrenal in Cushing’s syndrome, 166 hormonal diagnosis of, 149- 154, 169 radiography in, 154-164, 171 treatment of, 161-168 in virilism, 171 of renal arteries, 4, 14 Hypertension and atherosclerosis, 77, 80 and pheochromocytoma, 176 renovascular, 7S-109 angiotensin in, 76 aortography in, 3 arteriogram in, 92 bruits in, 80 calyceal filling in, 90-92 clinical characteristics of, 78- 80 creatinine concentration in, 95 diagnostic tests in, 82-100 glomerular filtration rate in, 92 Howard test in. 93-94 incidence of, 77-78 intravenous pyelogram in, 86- 92 juxtaglomerular cells in, 75, 81 nephrectomy in, 76 pathology of, 80-82 photoscanning in, 200 radioisotope renogram in, 84- 86, 190 Rapoport lest in, 95-96 sodium concentration in, 93 Stamey test in, 97-98 tubular rejection fraction ratio in, 95 unequal kidney size in, 86-89 urea infusion test in, 97-98 urine volume in, 93 spironolactone test in, 175 Ice %vater lest, 213, 277 Iliac artery, occlusive disease of, 16 Impotence, 255-267 causes of, 211, 213 cystoscopj’ in, 266 and early sexual experience, 258- 259 in female. See Frigidity 290 Index Impolcnce — Continued iatrogenic, 261 neural mechanisms in, 25^257 organic causes of, 260-263 and pro«tatilis, 266 ps>c}iogcnic, 262-263 xariclies of, 239 liKonlincncc Iccal, 2\0, 2"f> urinar), 209. 273 of nonrcsislance, 209, 275 o\crnow, 209, 275 psychologic, 209. 275 reflex, 209, 275 stress, 209, 273 Infarcts, kidney, pltoto«eaiinin|; of, 199 Infections, after biopsy, 131 Intcrscxuality, 232-231 chromatin tM in. 242-2tV classiflcation of, 235, 236, 2.37- 23fl criteria of sex, 233-231 cyMoscop) in, 210-211 0, 170, 172 iver*on-Koholm biopsy technique, 117 Juxtaglomerular cells of kidney, in hyj'crlen«ion, 75, fli Kark'Muclirckc-I’trani biopsy tnh- nique, 117-122 l7-Kt4ci*-\tTcihl c'xctttivvTj in androgenic hypersecretion, 169 cortisone afTecting, 170 in inlersexuality, 212 Kvtincy anomalies of, aortography in, 1 arterial blood supply of, 4-7 calyceal filling In liyiverlen«ion. 90-92 hvpcrlensien, renovascular, 7.>* 109 yvjxtaglomenilai tells In hypvfr* tension, 75. (11 nephrotoxicity alter aortography, 22-23 percutaneous needle hlojvsy of, 110-133 l>hoto«canning of, 192-202 jvolycyslic disease aortography in, I photoscanning in, 196 ptosis of, aortography in. 1 1, 20 radioisotope renogram, (.1, 104- 191 trauma of, aortography in, .3 luWrcuhrtis of, angiography in, 3 tumors of, abdominal venography in, 53 unequal sire of, in by 7 >erlcnsion. r.6-fi9 Index 291 Klinefelter’s syndrome, 232, 236, 238, 212 illustrative case of, 249 Loboiomy, incontinence after, 209, 275 Lymph node enlargements, abdom- inal venography of, 55, 59 Lymphography, 67-72 complications of, 72 indications for, 69-70 lechnifjue of, 67-68 Masturbation, guilt feelings in, 258 Mercury, chlormerodrin labeled with, 193 Metopirone. See SU-4S85 Micturition changes in, history of, 206-208, 273-274 initiation of, 207-208, 274 interruption of, 208, 274 precipitate, 207, 209, 275 sensations with, 206-207, 274 Miokon, radioiodinated, 192 IVephrectomy, in hj’pertension, 76 Neplirosclerosis, Howard lest in, 94 Nephrostomy, percutaneous needle, 49-53 Nephrotic syndrome, biopsy in, 112 Neurologic urology, 203-223 anesthesia of vesical mucosa, 219, 278 bladder mucosal perception studies, 218-219, 278 bowel instory, 210, 275-276 combined anesthesia, 220, 279 cystometry, 213, 277 cystoscopy, 218, 278 cystourelhrogram retragrade, 63, 214, 277 voiding, 63, 214, 277 examination, 220-222, 279-280 history, 205-213, 272-277 ice water test, 213, 277 incontinence types, 209, 275 laboratory data, 219, 278 pudendal nerve anesthesia, 219, 279 reflexes. 220-222, 279-280 residuum/capacity ratio, 217, 278 sensory studies, 222, 280 sexual history, 211-213, 276 sphincterometry, 214, 277 uroflomelry, 214-217. 277-270 urography, intravenous, 217, 278 urofogic procedures, 213-220, 277-279 voiding history, 206-208, 273- 274 NofCpinepKrine-producing tumors, 176, 177 Obesity, and Cushing’s syndrome, 149 Obsiruclion of bladder neck cjslograpljy in, 41-42 cystourethrography in, 63 ureteral antegrade pyelography in, 4-4 lymphography in, 67 radioisotope renogram in, 190 Occlusive arterial disease aortography in, 3 of iliac artery, 16 Oliguria, biopsy in, 112 292 Index Orgasm lt>«B o( in female, 213, 2c)Slic M of right kidnc), 197 horte^hoe kidnc), 197 h)jwrtension, reiio\a«cu!ar, 200 infarcts on kidney, 199 normal kidnc)s, 196 Piluilac) -adrenal interaction, 119- 151 J’neuningra/*h), rrlroperitoufal. in adrenal di«orders, \$5, I7J. 175 rtlinVdily of, 162-163 Poljejslic di»c4*e of kidiiejt aoDograph) In, \ photoK-anning of, 196 Pontocaine Bne«thpBia of »esical muco»3, 219, 2755 Prepnanewnilc'graplij in, 3 Tuliular rejection fraction ratio, 95 Tumors. See also Aflcnoma; Car- cinoma; PJicocliromocrIoma aiUenal aliclominal venograph} in, 53 amlograpliv in, 1 atroph} nith, 1C2 ktdno, aiidominal ^enngr8phv in, .55 relrnperiloncal nlidoTninai renngrapii) in, SS l)inphogfai>li) in, 67 Turner’s «)ndrome, 232, 236. 23fl, 212 I rca infu«ion te«t. in KsjK-rtcn*ion. renora*<;«laf. 97-93 Uremia, fiiops) in. 112, 111 (. rricr oli«lfuclion. See 01i*triiclion, ureteral rdrocatal, alniominni rrnograph) of. 50 l/rctlirographv. 02--67, See also Z\ sloureOirograpln Urinal*, Iii*lor> of utilization of, 203, 271 Urine residual, ami Madder capacitr, 217, 278 rolumeof, in rrno\3M:uInr hjper- tension. 93 Utoflomdrj, differential, 211-217, 277-270 Urograpliy, intra\enou*, 217, 278 in adrenal disorders, 1.51 reliaMlily of, 162-163 and reflux studies, dQ I'roKon, 22 in c) stograpliy, 36 radioiodinated, 181, 192 Vena ca\a visualization, 31-62 Venography, ol'dominal, 51-62 Ve*tcouiftrral trffux, 32—13, 211, 277 Nirilism, U)8-173, 2.31 endocrine differentiation in, 168- 172 radiograpliv in, 172 treatment of, 173 VM,\ if»t. in plieocliromoc)tciTna. 170 Voiding hi*tnr}, in neurologic ex- amination, 206-208, 273- 274